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PubMed1997

[Cisatracurium--is the stereoisomer an "ideal" relaxant? Histamine liberation and tryptase determination after bolus administration of cistracurium: a comparison with vecuronium].

UNLABELLED: Cisatracurium (51W89, Nimbex, Glaxo-Wellcome), an intermediate-acting non-depolarizing neuromuscular blocking agent, is a stereoisomer of atracurium. Histamine releasing propensities and serum tryptase level have been investigated after administration of cisatracurium (3 x ED95, 5 x ED95) or vecuronium (3 x ED90) in surgical patients. METHODS: After approval by our institutional review board, 62 patients (ASA I-II) were randomly assigned to three groups to receive either 3 x ED95 or 5 x ED95 cisatracurium, or 3 x ED90 vecuronium as a rapid bolus. A prick test was done the day before by scarification of the skin in the forearm. After premedication with 2 mg lormetazepam, anaesthesia was induced with thiopentone (4-12 mg/kg) and maintained with O2/N2O and isoflurane (1.5-2 vol.%). Six minutes after thiopentone, the patients received the relaxant and after further 6 min 0.1-0.2 mg fentanyl was given and the trachea was intubated. Heart rate (HR) and blood pressure (BP) were monitored every minute. Blood samples for histamine were withdrawn 5 min prior 3 and 5 min after each drug administration (thiopentone, relaxants). Plasma histamine was measured by radioimmunoassay (RIA) with a sensitivity of approximately 10 pg/ml. Additionally, serum tryptase was measured by RIA at baseline (-10 and -1 min) and 15 and 60 min after the relaxant administration. Levels for histamine > 1000 pg/ml and for tryptase > 2 micrograms/ml were considered significant. Cutaneous signs of histamine release were documented. RESULTS: Ten patients showed a positive prick-test reaction. Only after thiopentone some cutaneous signs (4 flush, 1 erythema) of histamine release were observed. There were no cutaneous signs of histamine release correlating with cardiovascular changes. Analysis of the blood samples demonstrated no significant increase in the histamine level in all three groups. Only in 1 patient was a significant higher histamine level (1133 pg/ml) measured 5 min after 5 x ED95 cisatracurium. All measurements of serum tryptase were within the physiological limits. DISCUSSION: In this study, with the particular time course of drug administration, neither cisatracurium nor vecuronium increased plasma histamine levels. Only after 5 x ED95 cisatracurium was 1 elevated histamine level documented after 5 min. In several studies increased histamine levels have been described, but without clinical manifestations. It is known that cutaneous signs can occur without increased plasma histamine levels due to the structural heterogeneity of mast cells. The cutaneous reactions in this study were caused by thiopentone. The tryptase values were within normal limits even in the patient with histamine release. No relationship between the positive results in the prick test and the incidence of cutaneous reactions and/or histamine release for drugs used in the induction of anaesthesia was observed. Whether cisatracurium has a potential for immunologic release is unknown.

Anesthesia, Intravenous↗
PubMed1989

Use of plasma histamine levels to monitor cutaneous mast cell degranulation.

A simple, minimally invasive procedure for monitoring cutaneous mast cell degranulation in vivo in man is described. Plasma histamine levels in venous blood draining the site of intradermal histamine, morphine, and antigen challenges were determined with a modified radioenzymatic assay. Elevations in plasma histamine above baseline levels of 0 to 0.6 ng/ml were measured after intradermal histamine; levels of 1.4 to 85.2 ng/ml were obtained after a 2 microgram intradermal challenge in 16 subjects. After antigen testing, peak plasma histamine levels ranged from 1.1 to 24.4 ng/ml (n = 9), and after morphine sulfate skin testing peak plasma histamine levels ranged from 2.3 to 12.7 ng/ml (n = 4). The time to achieve peak plasma histamine levels ranged from 2 to 10 minutes after histamine, from 5 to 15 minutes after antigen, and from 1 to 8 minutes after morphine challenges. Plasma levels returned to baseline within 30 minutes after histamine and morphine challenges but took more than 60 minutes for antigen challenges. With careful choice of the skin test site in relation to venous drainage, plasma histamine increases after either histamine or antigen were reproducible and reliable. Plasma histamine levels peaked 5 to 10 minutes before maximal development of the wheal-and-flare responses after histamine, antigen, or morphine skin tests. The wheal-and-flare skin tests continued to increase in magnitude despite rapidly declining plasma histamine levels. Thus skin tests eliciting reactions ordinarily seen in an allergist's office cause measurable increases in plasma histamine levels that can be used to directly monitor mast cell degranulation in man in vivo.(ABSTRACT TRUNCATED AT 250 WORDS)

Allergens↗
PubMedDate not supplied

The effects of histamine on rat and monkey retinal ganglion cells.

Mammalian retinas receive input from the posterior hypothalamus, and the neurotransmitter in this pathway is histamine. To determine whether histamine influences ganglion cells, we analyzed the effects of histamine on their maintained and light-evoked activity in vitro. In monkeys, histamine increased the maintained firing rate in 42% of ganglion cells, decreased it in 38%, and had no effect in 20%. When histamine and the HR3 agonist, methylhistamine, were applied to the same cells in succession, their effects were sometimes different, a finding suggesting that at least one other histamine receptor is present. In addition, the responses of some ganglion cells to full-field light stimuli were decreased by histamine and methylhistamine. In rats, the effects of histamine were somewhat different. Histamine increased the maintained firing rate of 82% of ganglion cells. Methylhistamine and the HR2 agonist, dimaprit, had the same effects as histamine. In some cells, histamine increased the light responses, but in others it decreased them. Histamine had no effect on ganglion cells in either species when synaptic transmission was blocked by low Ca2(+)/high Mg2+ Ames medium. Thus, the major effects of histamine were on the maintained activity of retinal ganglion cells. In both rats and monkeys, 80% or more of the ganglion cells were affected by histamine, and these responses were mediated by at least two of the histamine receptor subtypes.

Action Potentials↗
PubMed2006

Histamine inactivation in the colon of pigs in relationship to abundance of catabolic enzymes.

OBJECTIVE: Catabolism of histamine plays a crucial role in the intestine in preventing intoxication by luminal histamine. Two enzymes are involved, namely histamine N-methyltransferase (HMT) and diamine oxidase (DAO). The purpose of this study was to find a link between histamine catabolism and the activities of HMT and DAO. MATERIAL AND METHODS: Epithelia of porcine proximal colon were mounted in Ussing chambers. After mucosal addition of (3)H-histamine (100 micromol x l(-1)) and (14)C-mannitol, the appearance of non-catabolized histamine, (3)H-histamine label (hist-rad) and (14)C-mannitol label were measured in parallel on the serosal side. Activities of HMT and DAO were determined in the proximal colon and proximal jejunum. RESULTS: Differences between the fluxes of histamine and hist-rad indicated catabolic conversion of 81.4+/-1.6% histamine during epithelial transit. Fluxes of hist-rad and histamine increased linearly with increasing mannitol fluxes but the percentage of catabolized histamine was not related to either mannitol or hist-rad fluxes. However, the percentage of catabolized histamine rose with increasing DAO activity. Given a negative correlation between DAO and HMT activities, the fraction of catabolized histamine decreased with increasing HMT activity. HMT activity was comparable in the colon and jejunum, but DAO activity was approximately nine times higher in the jejunum. CONCLUSIONS: Permeation, but not the relative efficiency of catabolism, of histamine depends on epithelial/paracellular tightness. While previous studies have shown that colonic HMT essentially catabolizes the bulk of histamine during permeation, DAO activity seems to be more variable and limiting for the overall efficiency of the catabolic process.

Amine Oxidase (Copper-Containing)↗
PubMed1996

Mechanisms of prostaglandin F2 alpha and histamine-induced contractions in human chorionic vasculature.

We investigated the signaling pathways modulating histamine- and prostaglandin F2 alpha (PGF2 alpha)-induced contractions of human chorionic vasculature. Neomycin, a phospholipase C (PLC) inhibitor, attenuated PGF2 alpha and histamine contractile responses 40 and 60%, respectively. AIF4-, a G protein stimulant, induced a strong contraction alone but blocked histamine- and PGF2 alpha-induced contractions. Staurosporine (100 nM), a protein kinase C (PKC) inhibitor, attenuated the PGF2 alpha-dependent contractions by 50% but did not affect the histamine response. However, higher nonspecific inhibitory concentrations of staurosporine (1-2 microM) abolished histamine and PGF2 alpha contractile responses, presumably by inhibiting other protein kinases. Although, the PKC phorbol 12-myristate 13-acetate (PMA) did not affect basal tension or PGF2 alpha-dependent contractions, the histamine response was attenuated by 30%. Sodium nitroprusside (SNP), a guanylyl cyclase stimulant, strongly attenuated histamine- and PGF2 alpha-induced contractions. Tension increases were similarly attenuated by forskolin and isobutylmethylxanthine (IBMX), which increase intracellular cyclic AMP. In vessel rings prelabeled with [3H]myoinositol, PGF2 alpha and histamine increased [3H]inositol phosphate (IP) production 400 and 100%, respectively, indicating that PLC is stimulated by both agonists. Neomycin inhibited histamine- and PGF2 alpha-induced increases in [3H]IP production 60 and 40%, respectively. Staurosporine (0.1-1 microM) and PMA did not affect histamine- or PGF2 alpha-stimulated IP production. AIF4-alone increased IP production but blocked histamine- and PGF(2 alpha)-dependent IP increases. These observations suggest that at least part of the contractile responses due to PGF2 alpha and histamine are associated with stimulation of PLC through an AIF4(-)-sensitive G protein. The role of PKC is variable, because PGF2 alpha but not histamine tension responses were attenuated by PKC inhibition. In addition, therapeutic agents that increase cyclic AMP and cyclic GMP attenuated histamine- and PGF2 alpha-induced contractions in human chorionic vasculature, although histamine responses were relatively more sensitive to these agents.

Aluminum Compounds↗
PubMed1996

Regulation of the human histamine H1 receptor stably expressed in Chinese hamster ovary cells.

1. The human H1 receptor gene expressed in Chinese hamster ovary cells (CHOhumH1) encodes a classical histamine H1 receptor with a pharmacology similar to that of the H1 receptor found in guinea-pig cerebellum and the endogenously expressed human H1 receptor in 1321N1 astrocytoma cells as determined by [3H]-mepyramine binding studies. 2. In CHOhumH1 cells, histamine induced a concentration-dependent rise in inositol phosphates (EC50 2.23 +/- 0.97 microM) and a rapid increase of [Ca2+]i, followed by a sustained increase of [Ca2+]i upon addition of 100 microM histamine. 3. Short-term exposure of CHOhumH1 cells to histamine (100 microM) resulted in a decrease of subsequent histamine-induced Ca2+ responses. The histamine-induced desensitization appeared to be heterologous as the ATP-induced Ca2+ response was also found to be affected. 4. The process of heterologous histamine-induced desensitization of the Ca2+ response in CHOhumH1 cells can be ascribed to an alteration at the level of the intracellular Ca2+ pool, as the Ca2+ response of caffeine (10 mM), which releases Ca2+ from intracellular Ca2+ stores was also attenuated upon short-term histamine exposure. 5. In CHOhumH1 cells the PKC activator, PMA, was found to inhibit the histamine (100 microM)-induced Ca2+ response concentration-dependently (IC50 0.2 +/- 0.03 microM) as well as the ATP (100 microM)-induced Ca2+ response. However, this inhibition was only partial and less effective than histamine-pretreatment. Moreover, in CHOhumH1 cells PKC downregulation induced by long-term exposure to PMA (1 microM) did not affect the histamine-induced desensitization nor did pretreatment with the specific PKC inhibitor Ro-31-8220 (10 microM), indicating that in CHOhumH1 cells PKC is probably not involved in the heterologous desensitization. 6. Long-term treatment of CHOhumH1 cells with histamine or other H1 agonists resulted in a time- and concentration-dependent decrease in the number of H1 receptor binding sites (maximal reduction: 47 +/- 5%). 7. Long-term exposure of CHOhumH1 cells to ATP or PMA did not affect H1 receptor density. 8. Both histamine (100 microM)- and ATP (100 microM)-induced Ca2+ responses were affected upon long-term exposure of cells to histamine (100 microM), which might be explained by an alteration at a level distant from the receptor. 9. These results show that in CHOhumH1 cells the human histamine H1 receptor is susceptible to short-term and long-term receptor regulation in which PKC does not seem to play a role. The CHOhumH1 cells therefore provide an excellent model system for studying the mechanism(s) of PKC-independent H1 receptor regulation.

Animals↗
PubMed1989

Histamine and duodenal ulceration in renal transplant recipients.

Six of 25 renal transplant recipients had a duodenal ulcer at endoscopy. Histamine concentration and the activity of histamine methyltransferase, the degrading enzyme of histamine, were measured in gastric mucosal biopsies obtained at endoscopy and compared with patients with duodenal ulcer but not undergoing transplant and with patients with an apparently normal stomach and duodenum. Histamine concentrations in the corpus (no ulcer, median: 151 nmol/g; DU, median: 122 nmol/g) and in the antrum (no ulcer, median: 118 nmol/g; with DU, median: 113 nmol/g) of renal transplant patients, irrespective of ulcer diagnosis, and in patients with a chronic duodenal ulcer (median corpus histamine: 137 nmol/g and median antral histamine: 126 nmol/g) were not different from one another but significantly lower than the corresponding values in normal subjects (median corpus histamine: 241 nmol/g, p less than 0.01, and median antral histamine: 178 nmol/g, p less than 0.05). Histamine concentration in the corpus was significantly higher than in the antrum in all three groups of patients (p less than 0.05). There were no significant differences in histamine methyltransferase activity in any of the groups studied. Mucosal histamine and histamine methyltransferase activity were significantly correlated in the corpus (p less than 0.05) and antrum (p less than 0.02). Plasma concentration of histamine after transplant was higher in the patients who subsequently were discovered to have a duodenal ulcer (p less than 0.05). The occurrence of ulcer after transplantation was not related to the serum creatinine level. The uniform depletion of gastric histamine and increase in circulatory histamine after renal transplantation may be a factor in the pathogenesis of duodenal ulcer disease in this clinical situation.

Adult↗
PubMed2003

Histamine alters E-cadherin cell adhesion to increase human airway epithelial permeability.

During the immediate response to an inhaled allergen, there is an increase in the paracellular permeability of the airway epithelium.1 Histamine is an important agonist released during the immediate response to inhaled allergen. We hypothesized that histamine would increase human airway epithelial paracellular permeability and that it would do this by interrupting E-cadherin-based cell adhesion. Histamine, applied to the basolateral surface, increased the paracellular permeability of cultured human airway epithelia, and this effect of histamine was blocked by the histamine receptor antagonist promethazine. ECV304 cells express a histamine receptor, N-cadherin, and elements of the tight junction, including claudins, but they do not express E-cadherin. Histamine increased the paracellular permeability of ECV304 cells transfected with a vector and expressing E-cadherin but not ECV304 cells expressing lac-Z in the same vector. L cells do not express the histamine receptor, cadherins, or claudins. Histamine decreased adhesion of L cells expressing the human histamine receptor and E-cadherin to an E-cadherin-Fc fusion protein. Histamine did not alter the adhesion to the E-cadherin fusion protein of L cells expressing either the histamine receptor or E-cadherin alone. When applied to the apical surface, adenovirus poorly infects airway epithelial cells because its receptor, CAR, is restricted to the basolateral surface of the cells. When histamine was applied to the basolateral surface of airway epithelial cells, infection of the cells by adenovirus increased by approximately one log. This effect of histamine was also blocked by promethazine. Histamine increases airway paracellular permeability and increases susceptibility of airway epithelial cells to infection by adenovirus by interrupting E-cadherin adhesion.

Adenoviridae↗
PubMed2006

Histamine H1 receptor-stimulated interleukin 8 and granulocyte macrophage colony-stimulating factor production by bronchial epithelial cells requires extracellular signal-regulated kinase signaling via protein kinase C.

BACKGROUND: Histamine stimulates the release of several cytokines, such as interleukin (IL)-8 and granulocyte macrophage colony-stimulating factor, from bronchial epithelial cells. However, the functional individual histamine receptor subtype and intracellular signaling in bronchial epithelial cells are poorly defined. METHODS: Using human primary epithelial cells and the NCI-H292 cell line, we examined the expression of histamine receptor subtypes and histamine-induced second messenger. We also evaluated the involvements of mitogen-activated protein kinase, protein kinase C (PKC) and epidermal growth factor receptor in cytokine expression caused by histamine. RESULTS: Histamine H1 receptor (H1R) was the only subtype expressed in both types of cells. Histamine elevated intracellular calcium ion without affecting cAMP levels. Histamine induced the phosphorylation of extracellular signal-regulated kinase (ERK) 1/2. Histamine also phosphorylated PKC and myristoylated alanine-rich C kinase substrate. Ro-31-8220, a PKC inhibitor, and PD98059, a mitogen-activated protein/ERK kinase inhibitor, suppressed the histamine-induced ERK activation and the production of granulocyte macrophage colony-stimulating factor and IL-8. On the contrary, histamine had no effect on the phosphorylation of epidermal growth factor receptor, and its specific inhibitor AG1478 failed to inhibit the histamine-induced ERK activation. Olopatadine, an H1 antagonist, completely blocked the histamine-related responses, whereas H2 and H3 antagonists did not. Histamine also augmented the IL-8 production caused by IL-4 or tumor necrosis factor-alpha. CONCLUSIONS: The H1R-PKC-ERK pathway may play crucial roles in eliciting cytokine production from bronchial epithelial cells stimulated by histamine, leading to airway inflammation.

Bronchi↗
PubMed1975

Blood histamine levels and arteriovenous concentration differences after the intravenous administration of the basic compounds l-3 and 48/80 in the anaesthetized dog.

The effects of the i.v. administration of inulin trinicotinate-monomethochloride (L-3) on haemodynamics, airway pressure and blood histamine levels were studied in chloralose-anaesthetized dogs and compared with the effects of compound 48/80. The control arterial histamine level was 0.041 plus or minus 0.002 mug/ml (mean plus or minus SEM) as determined by a fluorometric assay. L-3 (0.15 mg/kg) released high amounts of histamine, as indicated by a peak level in arterial histamine of 0.212 plus or minus 0.027 mug/ml within 3 min, which was not futher enhanced on increasing the dosage of L-3 to 1 mg/kg. After the i.v. injection of 0.15 mg/kg of 48/80 the peak level in arterial histamine was 0.146 plus or minus 0.008 mug/ml, and the level was further markedly elevated to 0.918 plus or minus 0.068 mug/ml after the administration of 1 mg/kg of 48/80. The concomitant fall in systemic blood pressure and the rise in airway pressure can be satisfactorily explained on the basis of histamine liberation. Whereas these parameters as well as the blood histamine concentration gradually returned to control values, the heart rate remained elevated during the observation period of 2 h. The arteriovenous differences in blood histamine across various tissues and organs following L-3 and 48/80 administration indicated histamine release mainly from skin and muscle and histamine uptake by the kidney, the digestive tract and to a lesser extent the lungs. The portal-hepatic vein differences revealed no consistent changes in liver histamine balance. As regards the lungs and liver, the present results suggest a dynamic equilibrium between histamine release and uptake in these organs in the intact animal. Both, L-3 and 48/80 elicited a similar pattern of histamine release and uptake. The extreme histamine releasing capacity of 1 mg/kg of 48/80 may be explained by an additional non-selective mechanism of histamine liberation.

Airway Resistance↗
PubMed1990

Histamine-stimulated and GTP-binding proteins-mediated phospholipase A2 activation in rabbit platelets.

Histamine is known to be a mediator of inflammation. In order to understand the role of histamine in platelets, we have examined the effects of histamine on arachidonic acid (AA) release, cAMP accumulation, inositol trisphosphate production, and serotonin secretion. Incubation of rabbit (and human) platelets with histamine resulted in rapid increase of [3H]AA release from the platelets prelabeled with [3H]AA. The effect of histamine was blocked by the addition of H1 receptor antagonist mepyramine. Histamine did not substantially affect the cAMP content and inositol trisphosphate production. Histamine-stimulated AA release was not observed in digitonin-permeabilized platelets, whereas histamine acted synergistically with GTP or GTP analog, guanosine 5'-(3-O-thio)triphosphate. Histamine-stimulated, and GTP analog-dependent AA release was inhibited by guanosine 5'-(2-O-thio) diphosphate. The effects of three receptor stimulants, thrombin, norepinephrine, and histamine were both diminished by 1 microgram/ml of pertussis toxin treatment and by the antiserum against GTP-binding proteins (G proteins) treatment. However, the antiserum against beta gamma subunits of G proteins inhibited the histamine effect, not thrombin effect. 4 beta-Phorbol 12-myristate 13-acetate (PMA) treatment enhanced histamine-stimulated AA release and serotonin secretion but inhibited thrombin-stimulated reactions. The effect of PMA was dose dependent and was due to enhance the coupling of histamine receptors and G proteins. The results show the existence of H1 histamine receptors which couple phospholipase A2 activation via pertussis toxin-sensitive G proteins. Histamine actions differ in sensitivities to anti-beta gamma antiserum treatment and PMA treatment from thrombin actions.

Animals↗
PubMed1994

Subunit-specific potentiation of recombinant N-methyl-D-aspartate receptors by histamine.

Histamine has numerous functions in the brain and has recently been shown to modulate responses of N-methyl-D-aspartate (NMDA) receptors on hippocampal neurons by a mechanism that does not involve classical histamine receptors. In the present work, voltage-clamp recording was used to study the effects of histamine on recombinant NMDA receptors expressed in Xenopus oocytes, to determine whether histamine acts directly on NMDA receptors and to investigate the subunit specificity of the effects of histamine. Histamine potentiated responses to NMDA at heteromeric NR1/NR2 receptors containing splice variants of the NR1 subunit (NR1A or NR1E) that lack the amino-terminal insert, together with the NR2B subunit but not the NR2A or NR2C subunit. Stimulation by histamine (EC50 = 10 microM) had a novel profile, involving a rapid increase in the magnitude of NMDA-induced currents followed by slow (approximately 1-min) desensitization to a steady state level. Desensitization of the response to histamine was time dependent and could occur in the absence of receptor activation by NMDA. Stimulation by histamine was dependent on the concentration of agonist used to activate NR1A/NR2B receptors and was seen with high but not low concentrations of NMDA and glutamate. The effect of histamine was not blocked by classical histamine receptor antagonists but was mimicked by the histamine metabolite 1-methylhistamine. At a high concentration (1 microM) histamine produced a voltage-dependent inhibition of NMDA currents at NR1A/NR2B receptors and at receptors (NR1B/NR2B) that are not sensitive to stimulation by histamine. The results suggest that histamine acts directly at a novel recognition site on some subtypes of NMDA receptors to increase their activity.

Animals↗
PubMed1998

The role of histamine in platelet aggregation by physiological and immunological stimuli.

BACKGROUND: Platelets participate in allergic and inflammatory processes beside their role in haemostasis and thrombosis. This paper reports the level, the uptake, the metabolism and the release of histamine in human platelets. The effects of exogenous histamine, as well as the receptor and signal transduction of these effects, are also described. METHODS: Purified suspensions of platelets, prepared from healthy volunteers and from atopic patients, were exposed in vitro to physiological and immunological stimuli. Platelet aggregation was measured by the increase in light transmission; histamine content and release, as well as cytosolic free Ca2+ concentration, were measured fluorimetrically. Platelet histamine forming capacity, and the uptake of exogenous histamine, were measured with a radioisotopic method. RESULTS: Human platelets contain 72.5 +/- 9.6pmoles of histamine x 10(9) platelets, and their capacity to form histamine is 18.7 +/- 3.5pmoles h(-1)g(-1) protein, which is reduced by alpha-fluoromethylhistidine (10(-5) M) a selective inhibitor of the specific histidine decarboxylase. Human platelets take up the preformed amine by a calcium and energy-dependent process, and the uptake of histamine is reduced by mepyramine, an H1-receptor antagonist, and N,N-diethyl-2-[4-(phenylmethyl) phenoxyl] ethanamine (10(-6) M), a blocker of intracellular histamine receptors. Histamine is also metabolized by human platelets. The exposure of platelets to thrombin (10-60 mUml(-1)) produced a progressive aggregation, associated with histamine release. The same is observed in platelets isolated from atopic patients exposed to anti-IgE antibodies. Exogenous histamine dose-dependently potentiates the aggregation induced by physiological and immunological stimuli. In resting platelets cytosolic calcium level (207 +/- 4.2 nM/10(8) platelets) is increased by thrombin as well as by anti-IgE; this effect is potentiated by 10(-5) M histamine. CONCLUSIONS: The synergistic effect between histamine and other monoamines on platelet aggregation may explain some aspects of allergic vasculitis in which platelet aggregation is present.

Blood Platelets↗
PubMed1998

Histamine receptor subtypes mediating hyperpolarization in the isolated, perfused rat mesenteric pre-arteriolar bed.

Histamine is a general dilator of rat blood vessels. We investigated the relative contribution of receptor subtypes to the rat mesenteric dilator responses initiated by histamine and related agonists. Histamine initiated dose, and endothelium-dependent, dilation of constricted mesenteric beds with an ED50 of 0.4 +/- 0.1 nmol. The ED50 was increased 10-fold by 0.1 microM chlorpheniramine (a histamine H1-receptor selective antagonist). Histamine H2 receptor blockade with tiotidine (0.1 microM) slightly decreased, while thioperamide (1 microM), a selective histamine H3 receptor antagonist, did not block histamine-induced dilation. Mesenteric bed dilation initiated by histamine H2 receptor selective agonists, amthamine and dimaprit, were antagonized markedly by tiotidine. However, the dilation initiated by the putative histamine H3 receptor selective agonists, R(-)- or S(+)-alpha-methylhistamine and imetit were not affected by thioperamide (1 microM). Histamine H2- and H3-receptor mediated dilator effects were endothelium-independent and were blocked by either excess (80 mM) extracellular K+, or 1 mM tetrabutylammonium (a non-selective K+ channel blocker), as well as by 1 microM dequalinium, a non-peptide blocker of the small conductance Ca2+-activated (SKCa) K+ channels. We conclude that (i) histamine H1 receptor subtype predominantly mediates endothelium-dependent dilator effect of histamine, and (ii) vascular hyperpolarization through opening of K+ channels (SKCa) mediate the dilator responses to histamine H2 receptor (amthamine and dimaprit) and the putative histamine H3 receptor (R(-)-alpha-methylhistamine and imetit) agonists.

Animals↗
PubMed2000

Endothelium-independent relaxation induced by histamine in human dorsal penile artery.

1. In vitro preparations of human dorsal penile arteries were used to evaluate the effect of histamine and to characterize the histamine receptors involved in the response. 2. Cumulative administration of histamine induced a concentration-dependent relaxation in precontracted arteries. The H1 receptor agonist 2-pyridylethylamine induced a biphasic response: contraction followed by dilation. The H2 receptor agonist dimaprit produced a marked relaxation. Mepyramine, a histamine H1 receptor antagonist, led to a slight but statistically significant change in the pD2 value corresponding to the relaxant phase of the H1 receptor agonist and the histamine curve. The H2 receptor antagonist cimetidine induced a marked shift in the dimaprit concentration-response curve without affecting the maximum response. Incubation with cimetidine led to a considerable loss in the sensitivity of the arteries to histamine and in the maximum relaxation. Combined treatment with histamine H1 and H2 receptor antagonists resulted in an additional displacement compared with the effect of each antagonist alone on the histamine response. The effects observed using a histamine H3 receptor agonist and antagonist suggest that the involvement of this receptor is unlikely. 3. Removal of the endothelium was unable to reverse the histamine response. Pretreatment with NG-nitro-L-arginine methyl ester, L-arginine and indomethacin had no effect on the histamine control curve. 4. In conclusion, the vasodilation of human dorsal penile artery induced by histamine seems to be mainly mediated by muscular histamine H2 receptors, without the intervention of key intracellular mediators, such nitric oxide or relaxant prostanoids. A minor population of relaxant histamine H1 receptors cannot be excluded.

Adolescent↗
PubMed2003

Effects of amphotericin B and caspofungin on histamine expression.

STUDY OBJECTIVE: To determine the effects of amphotericin B deoxycholate and caspofungin on the release of histamine from human peripheral blood cells, mononuclear cells, and mast cells. DESIGN: In vitro cell culture experiments. SETTING: University medical center. MATERIAL: Cultured human mononuclear (THP-1) and mast (HMC-1) cells from five healthy volunteers. MEASUREMENTS AND MAIN RESULTS: The cultured cells were incubated with increasing concentrations of amphotericin B deoxycholate, diphenhydramine, amphotericin B deoxycholate plus diphenhydramine, caspofungin, caspofungin plus diphenhydramine, and the calcium ionophore A23187 for up to 24 hours. Histamine concentrations and histamine N-methyltransferase activity were determined at various time points throughout exposure. Cell viability was assessed by exclusion of erythrocin B. The A23187 increased histamine concentrations from baseline in peripheral blood and HMC-1 cells. No change in histamine concentrations was observed in response to amphotericin B deoxycholate, whereas caspofungin induced a significant increase in histamine release in peripheral blood cells and HMC-1 cells. No change in histamine concentrations was observed in THP-1 cells in response to any pharmacologic agent tested. Similarly, histamine N-methyltransferase activity in peripheral blood was not affected by amphotericin B deoxycholate, but was significantly decreased by caspofungin. CONCLUSION: Amphotericin B deoxycholate does not affect histamine concentrations or histamine N-methyltransferase activity in whole blood or HMC-1 cells, suggesting that the amphotericin B-induced infusion-related reaction is not a histamine-mediated event. Conversely, caspofungin increased histamine concentrations in whole blood and HMC-1 cells and inhibited histamine N-methyltransferase activity. These data suggest that infusion-related reactions associated with caspofungin may be mediated by histamine release secondary to caspofungin.

Amphotericin B↗
PubMed1993

Desensitization of histamine H1 receptor-mediated inositol phosphate accumulation in guinea pig cerebral cortex slices.

1. Histamine stimulated the production of [3H]-inositol phosphates in untreated (control) guinea-pig cerebral cortex slices with a best-fit EC50 of 17 +/- 4 microM, and a best-fit maximum response of 385 +/- 23% over basal accumulation. 2. Histamine pretreatment desensitized guinea-pig cortex slices to a subsequent challenge with histamine, which was observed as a reduction in the best-fit maximum response to 182 +/- 32% over basal accumulation. 3. The time-course for the histamine-induced production of [3H]-inositol phosphates was approximately linear over 90 min of stimulation in both control and histamine pretreated slices. The rate of production in pretreated slices was significantly slowed compared to control, such that by 90 min of histamine stimulation the desensitized slices produced 2.8 times the basal [3H]-inositol phosphate accumulation compared to 5.3 fold the basal [3H]-inositol phosphate accumulation in the control slices. 4. Displacement of [3H]-mepyramine binding to homogenates of guinea-pig cerebral cortex by mepyramine and histamine revealed that histamine pretreatment did not alter the apparent affinity of the H1 receptor for histamine (control Kd = 6.3 +/- 0.7 microM, desensitized Kd = 7.9 +/- 1.6 microM) or mepyramine (control Kd = 3.4 +/- 0.8 nM, desensitized Kd = 3.4 +/- 1.3 nM), nor was there any reduction in the calculated maximum number of [3H]-mepyramine binding sites (control Bmax = 192 +/- 31 fmol mg-1 protein, desensitized Bmax = 220 +/- 50 fmol mg-1 protein). 5. The histamine-mediated desensitization of response in guinea-pig slices was mediated by the HI receptor subtype, since the attentuated maximum histamine-stimulated [3H]-inositol phosphate accumulation could not be prevented by inclusion of an H2- (ranitidine) and an H3- (thioperamide) receptor antagonist during the pretreatment period.6. The desensitized histamine-stimulated [3H]-inositol phosphate accumulation recovered to 90% of control levels over a period of 150 min after the removal of the conditioning dose of histamine, with a half-time of recovery of about 95 min.

Animals↗
PubMed1997

Histamine release during cardiopulmonary bypass in neonates and infants.

PURPOSE: Histamine release has been previously documented in adults and children during cardiopulmonary bypass (CPB). It has not been studied in neonates nor during deep hypothermic circulatory arrest (DHCA). Histamine effects could explain many perioperative complications of congenital cardiac surgery such as dysrhythmias and massive oedema. Therefore, documentation of histamine release in the perioperative period is of clinical importance. The source of histamine can be determined by measurement of tryptase which is released with histamine from mast cells but not basophils. METHODS: Blood samples for histamine and tryptase were taken before and after specific events eg. cross-clamp removal, during anaesthesia and CPB in 14 infants and seven neonates undergoing complex congenital heart repairs and were analysed by commercial radioimmunoassays. Haemodynamic variables and pre and post-op weights were recorded to look for correlation between pathophysiological events and histamine release. RESULTS: Histamine concentration decreased at the start of bypass (0.69 to 0.38 ng.ml-1 at five minutes, (P < .005). There were no changes associated with DHCA and a small rise with reventilation (P < 0.02). Histamine concentration was lower in neonates than in infants (P < 0.05) during CPB. Plasma histamine and tryptase concentrations did not correlate, suggesting histamine release was from basophils and not from mast cells. Haemodynamic variables did not correlate with histamine concentrations. CONCLUSION: There was no major histamine release during CPB in infants and neonates. There was no relationship between histamine concentrations and clinical variables. Histamine released during CPB appears to come from basophils and may be a function of age.

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