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PubMed1983

Histamine modulation of human neutrophil oxidative metabolism, locomotion, degranulation, and membrane potential changes.

Previous reports have suggested that histamine modulates neutrophil chemotaxis, but this has not been observed by all laboratories. We have re-addressed this controversial point and demonstrate that histamine and H1- and H2-receptor-specific agonists cause limited inhibition of chemotaxis while stimulating chemokinesis. Furthermore, using the chemoattractant N-formyl-methionyl-leucyl-phenylalanine (f-met-leu-phe) as a stimulus, we demonstrate that histamine and H1/H2 agonists inhibit f-met-leu-phe-stimulated changes in membrane potential (monitored with the cyanine dye dipentyloxacarbocyanine), superoxide anion production (cytochrome c reduction), hydrogen peroxide formation (scopoletin fluorescence), and degranulation of granule contents (lysozyme and beta-glucuronidase) in a dose-dependent manner but have no effect on neutrophil functions stimulated by the secretagogues phorbol myristate acetate or A23187. All inhibitory effects of histamine and the H1/H2 agonists are reversed in a competitive manner by the H2 antagonist cimetidine. In addition, structure-activity studies using H1 and H2 receptor agonists and antagonists indicate that a single site with specificity for both H1 and H2 analogue structures modulates the various f-met-leu-phe-stimulated functions studied. Kinetic studies demonstrate that the inhibitory effects of histamine on neutrophil function are only observed when histamine is added before f-met-leu-phe and that inhibition occurs within 10 to 20 sec of histamine addition, does not persist after its removal, and is reversed by addition of cimetidine 10 to 20 sec before stimulation with f-met-leu-phe. Although the inhibitory effects of histamine are exerted early in the sequence of PMN activation by f-met-leu-phe, histamine does not affect the binding or internalization of f-met-leu-[3H]phe. The ability of histamine to modify the variety of neutrophil responses demonstrated in this report suggests an important and direct role for histamine in the regulation of inflammatory reactions in acute allergic settings or other disease states in which histamine release may occur.

Carbocyanines↗
PubMed1996

Dual control of human interleukin-2 and interferon-gamma gene expression by histamine: activation and suppression.

Histamine is considered to be an activator of cells with suppressive capacity. In agreement with this concept, we show that histamine elicits a strong inhibition of the induced expression of interleukin-2 (IL-2) and interferon-gamma (IFN-gamma) genes. However, our experiments reveal a novel property of histamine: early in the induction process, it strongly stimulates expression of these two genes in cultured human peripheral blood mononuclear cells (PBMC). The histamine-mediated superinduction of IL-2 mRNA is seen also in a Th cell line, showing that such cells respond directly to histamine. In the course of mitogenic induction, a 20-fold stimulation by histamine is converted into an equally strong inhibition. The response of a PBMC population to histamine thus undergoes a remarkable change following T cell activation. The dual effect of histamine can be blocked by the H2 histamine receptor antagonist cimetidine, while the early activation by histamine is mimicked by the H2 agonist impromidine, showing that both activation and inhibition of IL-2 and IFN-gamma gene expression by histamine are exerted via this receptor. These results support the concept that histamine, released during an immune response, exerts opposite regulatory effects by first activating cells able to express the IL-2 and IFN-gamma genes and only then suppressive cells that become responsive to histamine more slowly, but once activated shut off the expression of these genes.

Cells, Cultured↗
PubMed1985

Change of hepatic histamine content during hepatic fibrosis.

Hepatic function was studied by measuring the time courses of several variables in blood and liver using a chronic liver-injury model produced by administering CCl4 consecutively for 12 weeks in rats. A marked increase in liver histamine content occurred after 10 weeks of treatment with CCl4. At weeks 10 and 12, liver histamine levels in the CCl4-treated group were 1.95 and 4.61 times higher, respectively, than in the control group. This change in liver histamine content appeared after that in other variables such as glutamic pyruvic transaminase, alkaline phosphatase, and white blood cells, but it corresponded to a change in liver hydroxyproline. Increased mast cells were seen in fibrotic foci around Glisson's sheath by microscopic morphological observation of the liver 12 weeks after treatment with CCl4. The histamine concentration in plasma tended to decrease after CCl4 treatment, and at week 12 the decrease was statistically significant compared with control. The liver activities of histamine-metabolizing enzymes, histamine-N-methyltransferase and histaminase, decreased to 1/3.4 and 1/6.0 times those of the nontreated group, respectively, 12 weeks after treatment with CCl4, whereas blood histaminase increased about 9.2 times. The increase in histamine content in injured liver was presumedly derived from the increase in mast cells in the inflamed area of the liver; also, the deficiency of histamine-metabolizing enzymes in liver might have caused the high histamine content in the liver. On the other hand, the decrease in plasma histamine concentration might have occurred as a consequence of the enzyme leakage from hepatocytes that accompanied the breakdown of hepatocytes by CCl4 and thus, of the histamine metabolism in blood by the leaked enzymes. The same kind of experiment was performed using a dimethylnitrosamine-induced liver injury model in rats. The increase of hydroxyproline in the liver occurred 11 days after that of histamine content in liver. These results suggest the possibility that increased histamine in the liver may participate in the biosynthesis of collagen.

Animals↗
PubMed2001

Luminal Nalpha-methyl histamine stimulates gastric acid secretion in duodenal ulcer patients via releasing gastrin.

Nalpha-methyl histamine is an unusual histamine metabolite which is produced in the stomach infected by Helicobacter pylori and which was shown in animals to stimulate gastric acid secretion and to release gastrin in vitro isolated G-cells, but no information is available regarding its influence on gastric secretion and gastrin release in duodenal ulcer patients before and after H. pylori eradication. In this study, we compared the effects of intragastric administration of single or graded doses of Nalpha-methyl histamine on gastric acid secretion and plasma gastrin levels in 16 male duodenal ulcer patients (aging from 35 to 48 years and weighing 65-82 kg) before and after the eradication of H. pylori. Furthermore, the gastric luminal histamine and gastrin contents were determined before and after H. pylori eradication. In H. pylori-infected duodenal ulcer patients, the intragastric application of Nalpha-methyl histamine failed to affect gastric acid secretion or plasma gastrin levels. Following eradication of H. pylori, gastric luminal histamine and gastrin, and both basal gastric acid secretion and plasma gastrin levels, were significantly reduced. Nalpha-methyl histamine given intragastrically in graded doses to such H. pylori-eradicated duodenal ulcer patients was found to increase dose-dependently gastric acid output reaching at a dose of 5 mg, about 80% of histamine maximum induced by i.v. infusion of 25 microg/kg h of histamine dihydrochloride. We conclude that Nalpha-methyl histamine is a potent luminally active stimulant of gastrin release and gastric acid secretion in H. pylori-eradicated patients when luminal histamine is low but is not effective in H. pylori infected patients when luminal histamine is enhanced, possibly due to desensitization of gastrin (G-cells) and acid-producing (parietal) cells by Nalpha-methyl histamine produced excessively in H. pylori-infected stomach.

Adult↗
PubMed1996

Histamine release in sepsis: a prospective, controlled, clinical study.

OBJECTIVE: To determine if histamine release occurs in clinical sepsis. DESIGN: Prospective, controlled, clinical study. SETTING: Interdisciplinary intensive care unit and trauma ward. PATIENTS: Sepsis was confirmed in 20 patients (test group) by the criteria of the Veterans Administration Systemic Sepsis Cooperative Study Group (1987) and was verified by positive blood culture. In addition, patients were scored by the Elebute and Stoner Sepsis Score (1983), as modified by Dionigi et al (1985). A concomitant control group consisted of 20 postoperative patients with non-life-threatening trauma to the extremities and without signs of local or systemic infection. INTERVENTIONS: Observational study. Blood samples were collected for determination of plasma histamine concentrations in both groups at the time of study entry and on five succeeding days. MEASUREMENTS AND MAIN RESULTS: The patients were well matched, and the groups were not significantly different for all criteria known to influence histamine release. Comparison of the median values of each group on days 1 through 5 demonstrated significantly higher plasma histamine values in the test group on days 1 through 4, but these values were no longer significantly higher on day 5. While none of the nonseptic control patients achieved a plasma histamine concentration of > 1 ng/mL (the concentration of which was considered to be the pathologic cutoff point representing histamine release), these values (i.e., > 1 ng/ mL) were found in nine of 20 test group patients. In the test group, nonsurvivors (n = 9) had significantly higher plasma histamine concentrations than survivors (n = 11) throughout the whole study and eight of nine nonsurvivors showed a plasma histamine concentration of > 1 ng/mL. Correlation of plasma histamine concentrations on day 1 to sepsis severity (initial Sepsis Score) showed that all but one patient with a combined low Sepsis Score (< 20 points) and histamine concentration of < 1 ng/mL survived, while all patients with a Sepsis Score of > 20 points and histamine release (plasma histamine concentration of > 1 ng/mL) died. CONCLUSION: Increased histamine concentrations were shown to be causally associated (contributory determinant) with sepsis.

Adult↗
PubMed1989

Pharmacological characterization of histamine receptors in the human temporal artery.

1. The subtypes of histamine-receptors which mediate dilatation of small human temporal arteries have been characterized in vitro using 'selective' agonists and antagonists. 2. Dilatory responses were studied after preconstriction with prostaglandin F2 alpha since contraction was not seen at histamine concentrations up to 10(-4) M. Histamine caused a concentration-related relaxation of cerebral vessels with an IC50 value of 2.8 +/- 0.6 X 10(-7) M. 3. Cimetidine caused a parallel shift to the right of the histamine concentration-response curve whereas mepyramine was without observable effect. This suggests the presence of histamine H2-receptors only. However, combined treatment with mepyramine and cimetidine caused a more marked displacement of the concentration-response curve to the right. Schild analysis indicated that in situations of near complete blockade of the histamine H1-receptor subtypes, simple competitive antagonism at H2-receptors can be revealed with a pA2 value of 6.58 for cimetidine. The apparent pA2 value for mepyramine was 8.58. 4. The 'selective' H1-receptor agonists pyridylethylamine, 2-methylhistamine and thiazolylethylamine, and the H2-receptor agonists dimaprit, impromidine and 4-methylhistamine all mimicked the histamine response, but all except impromidine were less potent than histamine. The order of potency was impromidine greater than thiazolylamine greater than 4-Me-histamine greater than 2-Me-histamine greater than dimaprit greater than pyridylethylamine greater than tele-Me-histamine. 5. These results indicate that the histamine-induced dilatation in small human temporal arteries is mediated by both H1- and H2-receptors and that the latter subtype of histamine receptors predominates.

Adult↗
PubMed1992

Histamine-induced inhibition of neutrophil chemotaxis and T-lymphocyte proliferation in man.

Histamine inhibits in vitro human neutrophil chemotaxis and T-lymphocyte proliferation via H2 receptors. The aim of this study was to verify these inhibitory effects of histamine in man in vivo. Healthy volunteers were challenged with histamine by intravenous (1 mg), subcutaneous (1 mg) and inhalatory (2.4 mg) routes. Venous blood was taken before and at different times after challenge. Neutrophil chemotaxis was studied by the Boyden assay and T-lymphocyte proliferation by counting H3-thymidine incorporation in cultured mononuclear cells. Plasma histamine was measured by radioimmunoassay. Histamine infusion caused transient systemic symptoms as well as a significant decrease of neutrophil chemotaxis (mean - 26% +/- 6) and of PHA-pulsed T-lymphocyte proliferation (mean - 16% +/- 6) 4 h after histamine challenge. Subcutaneous injection of histamine caused only a significant decrease of neutrophil chemotaxis (mean - 24% +/- 15) 4 h after injection. Histamine inhalation was well tolerated and caused a significant depression of neutrophil chemotaxis (mean - 40% +/- 15) and of T-lymphocyte proliferation (mean - 27% +/- 6) 2 and 4 h after the challenge. Histamine challenges were always accompanied by a rapid and transient rise in plasma histamine. Inhalation of an H2 agonist (impromidine) but not of an H1 agonist (betahistine) caused a decrease of neutrophil chemotaxis and of T-lymphocyte proliferation. Oral pretreatment with an H2 antagonist (cimetidine) before histamine inhalation prevented histamine-induced decrease of neutrophil chemotaxis and T-lymphocyte proliferation, whereas astemizole, an H1 antagonist, had no effect. In conclusion, during the few hours following administration, exogenous histamine in man causes a depression of neutrophil chemotaxis and T-lymphocyte proliferation via H2 receptors.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Inhalation↗
PubMed1974

The release of histamine during gastric acid secretion in conscious rats.

1. Conscious gastric-cannulated rats were given [(3)H]histidine and aminoguanidine by dosage procedures intended to build up fast-turnover and slow-turnover pools of tissue [(3)H]histamine. Acid secretion was stimulated by I.V. infusion of pentagastrin, and the [(3)H]histamine content of gastric juice and excretion in urine were determined at 30 min intervals.2. The amount of [(3)H]histamine in gastric juice derived from either a slow-turnover or fast-turnover pool was very low in unstimulated animals, and was not altered during pentagastrin-stimulated acid secretion.3. From a slow-turnover pool pentagastrin caused increased urinary excretion of [(3)H]histamine. This was abolished by gastrectomy, so that the [(3)H]histamine liberated by pentagastrin from this pool appears to have been derived from the stomach. Evidence was not found for the existence of a slow-turnover histamine pool in the glandular mucosa of the stomach, and the source within the stomach of this pentagastrin-liberated histamine is thus uncertain.4. From a fast-turnover pool pentagastrin did not cause an increased urinary excretion of [(3)H]histamine. The amount of [(3)H]histamine excreted by gastrectomized rats was not different from that produced by gastric-cannulated animals. This suggests that a high proportion of urinary histamine derived from a fast-turnover pool was non-gastric in origin.5. Differences in the time scale of [(3)H]histamine release and acid secretion were not found. In some experiments the urinary output of [(3)H]histamine was prolonged beyond the end of pentagastrin administration and gastric acid secretion. However, the overall data do not suggest that urinary histamine output and gastric acid secretion take different time courses.

Animals↗
PubMed2005

The vagus regulates histamine mobilization from rat stomach ECL cells by controlling their sensitivity to gastrin.

The ECL cells in the oxyntic mucosa secrete histamine in response to gastrin, stimulating parietal cells to produce acid. Do they also operate under nervous control? The present study examines histamine mobilization from rat stomach ECL cells in situ in response to acute vagal excitation and to food or gastrin following vagal or sympathetic denervation. Applying the technique of microdialysis, we monitored the release of histamine by radioimmunoassay. Microdialysis probes were placed in the submucosa on either side of the stomach, 3 days before experiments. The rats were awake during microdialysis except when subjected to electrical vagal stimulation. One-sided electrical vagal stimulation raised serum gastrin and mobilized gastric histamine. However, gastrin receptor blockade prevented the histamine mobilization, indicating that circulating gastrin accounts for the response. Vagal excitation by hypoglycaemia (insulin) or pylorus ligation did not mobilize either gastrin or histamine. The histamine response to food was almost abolished by gastrin receptor blockade, and it was halved on the denervated side after unilateral subdiaphragmatic vagotomy. While the histamine response to a near-maximally effective dose of gastrin was unaffected by vagotomy, the response to low gastrin doses was reduced significantly. Abdominal ganglionic sympathectomy failed to affect the histamine response to either food or gastrin. In conclusion, gastrin is responsible for most of the food-evoked mobilization of ECL-cell histamine. The histamine response to electrical vagal stimulation reflects the effect of circulating gastrin rather than a direct action of the vagus on the ECL cells. Vagal denervation was accompanied by an impaired histamine response to food intake, probably reflecting the right-ward shift of the serum gastrin concentration-histamine response curve. The results suggest that the vagus controls the sensitivity of the ECL cells to gastrin.

Animals↗
PubMed2003

Histamine inhibits atrial myocytic ANP release via H2 receptor-cAMP-protein kinase signaling.

Changes in cyclic nucleotide production and atrial dynamics have been known to modulate atrial natriuretic peptide (ANP) release. Although cardiac atrium expresses histamine receptors and contains histamine, the role of histamine in the regulation of ANP release has to be defined. The purpose of the present study was to define the effect of histamine on the regulation of ANP release in perfused beating rabbit atria. Histamine decreased ANP release concomitantly with increases in cAMP efflux and atrial dynamics in a concentration-dependent manner. Histamine-induced decrease in ANP release was a function of an increase in cAMP production. Blockade of histamine H2 receptor with cimetidine but not of H1 receptor with triprolidine abolished the responses of histamine. Cell-permeable cAMP analog, 8-Br-cAMP, mimicked the effects of histamine, and the responses were dose-dependent and blocked by a protein kinase A (PKA)-selective inhibitor, KT5720. Nifedipine failed to modulate histamine-induced decrease in ANP release. Protein kinase nonselective inhibitor staurosporine blocked histamine-induced changes in a concentration-dependent manner. KT5720 and RP-adenosine 3',5'-cyclic monophosphorothioate, another PKA-selective inhibitor, attenuated histamine-induced changes. These results suggest that histamine decreases atrial ANP release by H2 receptor-cAMP signaling via PKA-dependent and -independent pathways.

Animals↗
PubMed2000

Histamine H(2) receptor activated chloride conductance in myenteric neurons from guinea pig small intestine.

Whole cell perforated patch-clamp methods were used to investigate ionic mechanisms underlying histamine-evoked excitatory responses in small intestinal AH-type myenteric neurons. When physiological concentrations of Na(+), Ca(2+), and Cl(-) were in the bathing medium, application of histamine significantly increased total conductance as determined by stepping to 50 mV from a holding potential of -30 mV. The current reversed at a membrane potential of -30 +/- 5 (SE) mV and current-voltage relations exhibited outward rectification. The reversal potential for the histamine-activated current was unchanged by removal of Na(+) and Ca(2+) from the bathing medium. Reduction of Cl(-) from 155 mM to 55 mM suppressed the current when the neurons were in solutions with depleted Na(+) and Ca(2+). Current-voltage curves in solutions with reduced Cl(-) were linear and the reversal potential was changed from -30 +/- 5 mV to 7 +/- 4 mV. Niflumic acid, but not anthracene-9-carboxylic acid (9-AC) nor 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid (DIDS), suppressed the histamine-activated current. A membrane permeable analogue of cAMP evoked currents similar to those activated by histamine. A selective histamine H(2) receptor agonist (dimaprit) mimicked the action of histamine and a selective histamine H(2) receptor antagonist (cimetidine) blocked the conductance increase evoked by histamine. A selective adenosine A(1) receptor agonist (CCPA) reduced the histamine-activated current and a selective adenosine A(1) receptor antagonist (CPT) reversed the inhibitory action. The results suggest that histamine acts at histamine H(2) receptors to increase Cl(-) conductance in AH-type enteric neurons. Cyclic AMP appears to be a second messenger in the signal transduction process. Results with a selective adenosine A(1) receptor agonist and antagonist add to existing evidence for co-coupling of inhibitory adenosine A(1) receptors and histamine H(2) receptors to adenylate cyclase in AH-type enteric neurons.

1-Methyl-3-isobutylxanthine↗
PubMed1990

Enhanced prostaglandin synthesis after ultraviolet injury is mediated by endogenous histamine stimulation. A mechanism for irradiation erythema.

Acute ultraviolet light B (UVB) injury is associated with dermal mast cell histamine release. The possibility that histamine-stimulated prostaglandin (PG) synthesis could be a mechanism for irradiation erythema was therefore examined using human skin explants. Explants responded to UV irradiation (120 mJ/cm2) with a fivefold increase in synthesis of prostaglandins E2, F2 alpha and 6-keto PGF1 alpha. Incubating explants with the H1 antihistamines brompheniramine (50 microM) or pyrilamine (30 microM) inhibited PG release from irradiated explants 63 +/- 4.9% (mean +/- SEM) 6 h after UV exposure. Antihistamines did not affect PG synthesis in control explants. Irradiation increased the histamine concentration in explant conditioned medium only 50% over basal values, suggesting that irradiation enhanced histamine responsiveness. Explants were therefore incubated with exogenous histamine. In irradiated explants, PG synthesis was stimulated threefold by 3 microM histamine. Unirradiated explants' PG synthesis was unaffected by histamine. Enhanced histamine sensitivity was also examined in epidermal cell cultures. In irradiated cultures, histamine sensitivity was again markedly potentiated: as little as 1 microM histamine stimulated significant PGE2 release and the response to 10-30 microM histamine was increased six to eight times compared with that of unirradiated cultures. These studies demonstrate that endogenous histamine stimulates PG synthesis in human skin after UV injury by potentiation of histamine-induced prostaglandin release. Potentiated agonist responses induced by UV exposure may contribute to the effects of UVB irradiation injury and in particular to irradiation erythema.

Animals↗
PubMed2003

[Physiological function mediated by histamine synthesis].

Histamine is involved in a variety of physiologic responses, such as inflammation, type I allergy, gastric acid secretion, and neurotransmission. Previous studies have focused on specific receptors for histamine and histamine release through degranulation, and the regulation of histamine synthesis and its physiologic roles remain to be clarified. We have studied histidine decarboxylase (HDC), the rate-limiting enzyme for mammalian histamine synthesis. Immunocytochemical approaches with an anti-HDC antibody revealed that histamine synthesis occurs in two distinct compartments of mast cells, cytosol and granules, and is regulated by the posttranslational processing of HDC. We also found that histamine synthesis in mast cells is markedly induced by IgE even in the absence of antigens, which may be relevant to enhanced responses of mast cells under allergic conditions. We then developed HDC-deficient mice by gene targeting to investigate the physiologic roles of histamine. We not only confirmed that histamine is essential for type I allergy and stimulates gastric acid secretion, but also found that histamine may regulate the proliferation and differentiation of mast cells. Furthermore, in HDC-deficient mice histamine produced by infiltrated neutrophils can suppress the production of antitumoral cytokines, such as interferon-gamma and tumor necrosis factor-alpha through H2 receptors in the tumor tissues. In this review, we describe recent topics in histamine research, including our results focusing on histamine synthesis and its physiologic roles.

Animals↗
PubMed1991

Effect of the histamine-1 antagonist astemizole alone or with omeprazole on rat gastric mucosa.

The stimulation of acid secretion by gastrin may in the rat be explained solely by gastrin-induced histamine release. This study was done to examine whether histamine could mediate the general trophic effect of gastrin on the oxyntic mucosa, by using a long-acting selective histamine-1 antagonist (astemizole) alone or with omeprazole-induced hypergastrinaemia for 90 days in female Sprague-Dawley rats. At day 90, isolated vascularly perfused rat stomachs were prepared to study maximal gastrin- and histamine-stimulated acid and pepsinogen outputs and maximal gastrin-stimulated histamine release. Oxyntic mucosa morphometry, mucosal histamine and pepsinogen contents, and plasma gastrin and histamine levels were also determined. For the first time, omeprazole has been found to inhibit gastric emptying and to increase plasma histamine. As compared with controls, astemizole alone did not influence plasma gastrin, increased plasma histamine in only some rats, and gave a slight increase in all other variables. Together with omeprazole, it further increased variables already stimulated by omeprazole. Thus, mucosal thickness, histamine concentration, and chief-cell density in oxyntic mucosa were significantly higher in astemizole/omeprazole-treated rats than in omeprazole-treated rats. Gastrin-stimulated histamine release was increased in both astemizole- and omeprazole-treated rats. For all rats plasma histamine was significantly correlated with plasma gastrin and with numerical fundic argyrophil cell density. In conclusion, the present study confirms the trophic effect of gastrin and shows a slight trophic effect of astemizole on the oxyntic mucosa. It also shows that plasma histamine may reflect the argyrophil cell density in the oxyntic mucosa and that omeprazole inhibits gastric emptying.

Animals↗
PubMed1992

Histamine release and SOD, allopurinol and ranitidine pretreatment in haemorrhagic shock in the rat.

Histamine release have been demonstrated in haemorrhagic shock. There are some observations that oxygen free radicals can cause histamine release. Oxygen free radicals play a role in the pathogenesis of gastric mucosal lesions. The goal of this study was to determine whether ranitidine or SOD and allopurinol pretreatment modify the histamine release during and after the haemorrhagic shock in the rat. In the anaesthetized rat 0.1 N HCl was instilled into the stomach and the rat was bled to reduce the blood pressure to 30 mmHg for 20 min. The shed blood was reinfused. Twenty min later the stomach was removed. The area of gastric mucosal lesions were measured, histological grading was made. Blood samples taken from the carotid artery were examined by radioimmunoassay (IMMUNOTECH) to determine the plasma histamine level. Plasma histamine level did not change significantly during the preparative surgery, but there was a significant increase of histamine level by the end of shock period. After the reinfusion of the blood the plasma histamine remained essentially at the same level for five min. Oxygen free radicals did not cause an important histamine release. By the end of the experiment the histamine level decreased dramatically. Ranitidine, allopurinol and SOD pretreatment provided significant protection against the gastric mucosal lesions. Allopurinol and SOD did not influence significantly the histamine level. Ranitidine caused significant histamine release immediately after the injection and every histamine value was significantly higher in this group except for the final value which was lower than the control one. The oxygen free radicals were not found as endogenous histamine releasers in this study.

Allopurinol↗
PubMed1990

Inotropic, electrophysiological and biochemical responses to histamine in rabbit papillary muscles: evidence for coexistence of H1- and H2-receptors.

This study was performed to determine the subtypes of histamine receptors that are involved in the electrophysiological, inotropic and biochemical responses to histamine in isolated rabbit papillary muscles. Histamine increased force of contraction and shortened action potential duration (APD) in a concentration-dependent manner. The former was antagonized by chlorpheniramine, a H1-antagonist, whereas the latter was blocked by cimetidine, a H2-antagonist. However, even when H1-receptors were blocked entirely by chlorpheniramine, histamine still produced a positive inotropic effect, an effect which was antagonized by cimetidine. On the other hand, when H2-receptors were eliminated by cimetidine, histamine caused a H1-receptor mediated APD prolongation. Carbachol attenuated the decrease in APD but not the increase in force of contraction caused by histamine. Cyclic AMP and cyclic GMP levels both were elevated significantly by histamine. The increase in cyclic AMP level induced by histamine was abolished by cimetidine, but not altered by chlorpheniramine, whereas the converse was true for the increase in cyclic GMP level. Additionally, histamine produced a significant stimulation of phosphoinositide hydrolysis as measured by [3H]inositol monophosphate accumulation, although its extent was far less than that produced by carbachol. The phosphoinositide response to histamine was blocked by chlorpheniramine. These data suggest that H1- and H2-receptors coexist in rabbit ventricles. Stimulation of H1- and H2-receptors with histamine independently sets off the biochemical responses linked specifically to the respective subtypes of histamine receptors. On the other hand, the inotropic and electrophysiological responses to histamine are governed predominantly by H1- and H2-receptors, respectively, and this results in an apparent restriction of the expression of the responses mediated by another subtype.

Action Potentials↗
PubMed1988

[Immunoenzyme assay for histamine].

In order to produce monoclonal antibody to histamine, mice are immunized with histamine conjugated to bovine serum albumin (BSA) by the 1,4-benzoquinone method. After an initial screening using ovalbumin (OVA) and histamine-OVA conjugate as antigens to identify monoclonal antibody secreting clones, the hybridomas are isolated by limiting dilution cloning and grown in ascites. The specificity of selected monoclonal antibody (D22) is studied using a direct enzyme immunoassay and an ELISA-inhibition test. D22 antibody reacts with histamine-protein conjugates prepared by the 1,4-benzoquinone coupling procedure. On the contrary, this antibody is unreactive with native proteins, 1,4-benzoquinone treated proteins or various amine-protein conjugates. Free unconjugated histamine significantly inhibits antibody binding to histamine-OVA and 50% inhibition (IC50) is recorded at 5 X 10(-3) M. On a histamine molar concentration basis a much more lower inhibitory potency of free histamine is recorded, as compared to histamine-benzoquinone derivative (IC50 = 2 X 10(-8) M) and to histamine-OVA (IC50 = 7 X 10(-10) M). It is our interpretation that for the D22 antibody, the main epitope encompasses the 2-histaminyl-1,4-benzoquinone moiety and that this points to the importance of polyvalent ligands for efficient bivalent binding of the IgG antibodies. Using the D22 antibody we set up a competitive enzyme immunoassay for measuring histamine in various biological samples. In this assay, the histamine to be quantified is chemically modified by 1,4-benzoquinone and allowed to compete with a histamine-peroxidase conjugate for binding to a limited amount of monoclonal antibody which is used to coat the wells of a microtitration plate.(ABSTRACT TRUNCATED AT 250 WORDS)

Antibodies, Monoclonal↗
PubMed1989

[Radioimmunometric determination of histamine in myeloproliferative syndromes].

Quantitative analysis of histamine is increasingly used in clinical haematology. The present study demonstrates the properties of and potential indication for a novel histamine radioimmunoassay (RIA) in clinical haematology. The sensitivity of this test assay corresponds to a histamine level of 0.1 to 0.5 nM, the non-specific cross reaction with endogenous histamine metabolites appears to be less than 0.1%. The total histamine levels in the peripheral blood of healthy donors (n = 10) ranged from 10 to 100 ng/ml, the plasma histamine values from 0.02 to 0.6 ng/ml blood. Increased levels of total histamine were measured in myeloproliferative syndromes, i.e. in patients with chronic myeloid leukemia (CML) (8 of 9), myelofibrosis (OMS) (2 of 4), and polycythaemia vera (PCV) (1 of 2). An excessive increase in total histamine was observed in healthy rhesus monkeys (n = 10) treated with recombinant human interleukin-3 (rhIL-3). The total histamine value correlated with the absolute number of circulating blood basophils (correlation coefficient: 0.9). The calculated content of histamine per basophil was found to be 0.5 to 1.5 pg. Plasma histamine values in patients suffering from myeloproliferative syndromes were within the normal range. In contrast, a moderate to marked increase in plasma histamine values was observed in monkeys during IL-3 treatment. The radioimmunometric analysis of histamine clearly represents a useful new test system in clinical haematology, especially in the follow up of malignant as well as IL-3-induced myeloproliferation.

Animals↗