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PubMed1987

Histamine H1 receptors on adherent rheumatoid synovial cells in culture: demonstration by radioligand binding and inhibition of histamine-stimulated prostaglandin E production by histamine H1 antagonists.

Histamine H1 receptors have been demonstrated on adherent rheumatoid synovial cells using biochemical and radioligand binding assays in vitro. The addition of histamine (17.8 mumol/l) to nine primary cultures of adherent rheumatoid synovial cells resulted in a two- to 21-fold increase in the production of prostaglandin E (PGE). This increase was inhibited by three H1 receptor antagonists (mepyramine, tripelennamine, and chlorpheniramine) in a dose related manner at concentrations below 10(-6) mol/l. Competitive binding assays with [3H]mepyramine gave ED50 values of approximately 10(-5) mol/l for the three H1 antagonists. H2 receptor antagonists (cimetidine and ranitidine) did not inhibit the histamine induced increase in PGE and did not compete effectively with the binding of H1 antagonists.

Arthritis, Rheumatoid↗
PubMed1983

Histamine is able to suppress the inhibitory effect of somatostatin on exogenous gastrin: comparison between extractive antral histamine and synthetic histamine.

In view of examining inhibition by somatostatin of gastrin-induced gastric secretion, antral histamine (AH) and synthetic histamine (SH) were comparatively studied in dogs. Both AH and SH were able to antagonize somatostatin: their potencies did not differ significantly as regards acid secretion, but AH is more potent than SH on pepsin secretion. The dose-dependent activity of AH was limited for the period of infusion. The denervated pouch is more sensitive than the innervated stomach. We suggest that antral histamine might intervene in the complex regulation of gastric secretion where somatostatin and gastrin act antagonistically and where the stimulatory as well as inhibitory fibers of the vagus intervene.

Animals↗
PubMed1977

Histamine-releasing effect of a corticotrophin derivative. I. Histamine-releasing effect of a nonadecapeptide in comparison with that of other histamine liberators.

The histamine-liberating properties of a synthetic polypeptide (an a synthetic polypeptide (an alkylprolyl derivative of beta1-19-corticotrophin) were investigated under a variety of experimental conditions. It was found to be more potent in this respect than Compound 48/80, Melittin and Triton X-100. The degree of cell destruction observed in conjunction with the release of histamine induced by C 44 680-Ba suggests that the mode of action of the substance more closely resembles that of Compound 48/80 than that of Triton.

Adrenocorticotropic Hormone↗
PubMed1993

Responses of anterior pituitary hormones and hypothalamic histamine to blockade of histamine synthesis and to selective activation or inactivation of presynaptic histamine H3 receptors in stressed rats.

The stress-induced release of anterior pituitary hormones and changes in hypothalamic content of histamine (HA) and its metabolite tele-methylHA (t-meHA) were studied in male rats during inhibition of HA synthesis or activation or blockade of HA H3 receptors. Pretreatment with the HA synthesis inhibitor alpha-fluoromethylhistidine (alpha-FMH; 200 micrograms intracerebroventricularly (icv) at -120 min) or the specific H3 receptor agonist R(alpha)methylhistamine (RmHA; 10 mg/kg intraperitoneally (ip) at -180 and -60 min) inhibited by 30-80% the responses of prolactin (PRL), corticotropin (ACTH) and beta-endorphin (beta-END) immunoreactivity to 1, 2.5 or 5 min of restraint stress (p < 0.05-0.01), but had no effect on basal secretion of the hormones. The inhibitory effect of the H3 receptor agonist RmHA (10 mg/kg x 2) on the hormone response to 5 min of restraint stress was prevented by simultaneous ip administration of the H3 receptor antagonist thioperamide. alpha-FMH reduced the hypothalamic content of HA 60% and that of t-meHA 30%, while RmHA had no effect on the HA content. Restraint stress for 5 min did not affect the HA and t-meHA contents, which may be due to the short duration of stress exposure. Pretreatment with the H3 receptor antagonist thioperamide (5 or 10 mg/kg ip at -120 min) had no effect on basal or restraint stress-induced release of PRL, ACTH or beta-END, although the compound increased the hypothalamic content of t-meHA 2-fold.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenocorticotropic Hormone↗
PubMed1995

Histamine chloramines have a persistent stimulating effect on histamine H2 receptors and gastric acid secretion.

Histamine plays an important role in the control of gastric acid secretion. Recently, chlorinated derivatives of histamine have been identified as having multiple effects on the intestinal tract. The aim of this study was to investigate the role of histamine chloramines on gastric acid secretion. We compared the effects of histamine and histamine chloramines on the histamine H2 receptors in vitro using guinea pigs and on gastric acid secretion in rats. With respect to the effects on histamine H2 receptors, histamine monochloramine showed agonist effects similar to those seen with histamine, but the agonist effects of histamine dichloramine were about half those of histamine. Unlike histamine effects, the histamine H2 receptor agonist effects of histamine monochloramine and histamine dichloramine did not disappear after repeated washout. With respect to the stimulation of gastric acid secretion in vivo, histamine monochloramine was similar to histamine, while the effect of histamine dichloramine was 42.2-52.7% of that of histamine. The recovery time to the basal secretory level after completion of stimulation by histamine chloramines was significantly prolonged compared with histamine. These results suggest that histamine chloramines, which bind strongly with histamine H2 receptors, may delay the termination of gastric acid secretion and increase the burden on the gastric and duodenal mucosa.

Animals↗
PubMed2004

Role of capsaicin-sensitive nerves and histamine H1, H2, and H3 receptors in the gastroprotective effect of histamine against stress ulcers in rats.

UNLABELLED: It is assumed that an overproduction of gastric acid is the most important factor in the development of peptic ulcer. However, it has been also demonstrated that gastric defense mechanisms, which prevent mucosal injury, are enhanced by the same factors that increase acid secretion. The aim of this study was to examine the role of capsaicin-sensitive sensory nerves and histamine H1, H2, and H3 receptors in histamine-induced gastroprotection against stress ulcers. Studies were performed on rats with intact or ablated sensory nerves. Ablation of sensory nerves was induced by neurotoxic doses of capsaicin. Gastric ulcers were induced by water immersion and restrain stress. Before exposure to stress, rats were pretreated with saline (control), histamine (10 micromol/kg), histamine H1 receptor antagonist pyrilamine (100 micromol/kg), histamine H2 receptor antagonist ranitidine (100 micromol/kg), histamine H3 receptor antagonist thioperamide (100 micromol/kg), or a combination of histamine with these histamine receptor antagonists. RESULTS: Histamine alone reduced ulcer area evoked by stress and this effect was accompanied by an increase in gastric mucosal blood flow and mucosal DNA synthesis, as well as a decrease in serum pro-inflammatory interleukin-1beta concentration. Treatment with combination of pyrilamine plus histamine caused an increase in gastric ulcer area and serum interleukin-1beta above the value observed in animals treated with saline, and this effect was accompanied by a decrease in gastric mucosal DNA synthesis. Ranitidine, in combination with histamine, reduced the ulcer area and serum interleukin-1beta to a minimal value, whereas gastric mucosal blood flow and DNA synthesis reached a maximal value. Pretreatment with thioperamide before histamine administration abolished the histamine-evoked reduction in gastric ulcer area. Ablation of sensory nerves increased the ulcer area in animals treated with saline or histamine, or histamine in combination with pyrilamine or ranitidine. In animals with sensory nerves ablation combined with administration of thioperamide plus histamine, the ulcer area was similar to that in saline-treated animals with intact sensory nerves. We conclude that: (1) histamine exhibits protective effect against stress-induced gastric ulcer and that this gastroprotection is related to stimulation of histamine H1 and H3 receptors; (2) blockade of histamine H2 receptors exhibited beneficial effect on gastric mucosa against stress-induced gastric ulcers; and (3) ablation of sensory nerves aggravates stress-induced gastric ulcer and reduces histamine-evoked gastroprotection related to stimulation of histamine H3 receptors.

Animals↗
PubMed1985

Histamine modulates contraction and cyclic nucleotides in cultured rat mesangial cells. Differential effects mediated by histamine H1 and H2 receptors.

Histamine influences the glomerular microcirculation and modulates immune-inflammatory responses. In the rat kidney, histamine is synthesized by glomeruli and stimulates cyclic nucleotide production specifically in glomeruli. We investigated the in vitro effect of histamine on cyclic nucleotide accumulation in rat cultured glomerular mesangial and epithelial cells. Histamine stimulated cyclic AMP (cAMP) accumulation in cultured mesangial cells (64.0 +/- 22.1 to 511.4 +/- 86.6 pmol/mg protein, n = 9) but had no effect on cAMP accumulation in epithelial cells. This effect was dose-dependent and time-dependent. Stimulation of cAMP accumulation occurred in the range of 5 X 10(-6) M-10(-4) M histamine with a half maximal stimulatory effect of 2 X 10(-5) M. Initial stimulation was noted by 30 s, and maximum stimulation was observed at 5 min. The H2 antagonist cimetidine (10(-4) M) abolished the stimulatory effect of histamine (10(-4) M), while equimolar concentrations of the H1 antagonist diphenhydramine had no significant effect on cAMP accumulation. Moreover, the specific H2 agonist dimaprit, but not the H1 agonist 2-pyridylethylamine, stimulated cAMP accumulation. Histamine had no effect on cAMP accumulation in epithelial cells or on cyclic guanosine monophosphate accumulation in epithelial or mesangial cells. Since the in vivo infusion of histamine reduces ultrafiltration coefficient and since mesangial cell contraction is thought to be responsible for the reduction in the ultrafiltration coefficient, we examined the effect of histamine on the contractile property of mesangial cells. Histamine (5 X 10(-6)-10(-4) M) contracted mesangial cells, and the H1 antagonist diphenhydramine (10(-4) M) but not the H2 antagonist cimetidine (10(-4) M) prevented histamine (10(-4) M) induced contraction. In addition, the H1 agonist 2-pyridylethylamine, but not the H2 agonist dimaprit, contracted mesangial cells. Histamine and its specific agonists and antagonists induced contraction of isolated glomeruli as assessed by glomerular planar surface area in a manner parallel to their effect on mesangial cells. Cinnarizine (10(-5) M), a Ca++ channel blocker, or Ca++, Mg++-free medium prevented histamine (10(-4) M) induced mesangial cell and glomerular contraction. Thus, histamine enhances cAMP accumulation specifically in mesangial cells via an H2 receptor. In contrast, histamine contracts mesangial cells and glomeruli via an H1 receptor, an effect that is dependent on extracellular Ca++ entry. These findings show that histamine potentially influences intraglomerular hemodynamics via effects on mesangial cell contraction. Moreover, our findings considered with the in vivo observation that histamine reduces kf via and H1 receptor provide further support of the hypothesis that mesangial cell contraction regulates the glomerular capillary surface area available for filtration. Our studies also show that this contractile effect of histamine is dependent on extracellular calcium. The presence of a cAMP system sensitive to histamine may have major implications in the pathogenesis of inflammatory glomerulopathies. Mesangial cells possess characteristics similar to circulating and tissue immune effector cells, including lysosomal enzyme release, oxygen radical production, and release of a number of immunomodulatory factors. Histamine and cAMP have been shown to modulate such characteristics of inflammatory cells. It is therefore conceivable that histamine, via its interaction with H2 receptors and subsequent generation cAMP, may have profound effects on such properties of mesangial cells, suggesting that this autacoid may modulate not only glomerular hemodynamics but also immune, inflammatory responses within the glomerulus.

1-Methyl-3-isobutylxanthine↗
PubMed1994

Characterization of the histamine receptors in the guinea-pig lung: evidence for relaxant histamine H3 receptors in the trachea.

1. The histamine receptors were characterized on isolated circular segments of trachea and pulmonary arteries from the guinea-pig. The motor responses to histamine H1-, H2- and H3-receptor agonists and antagonists were tested and the responses obtained were analysed in relation to the respiratory epithelium and the vascular endothelium. 2. Histamine induced a biphasic response in trachea and in pulmonary arteries. In low concentrations, histamine acted as a potent relaxant agent of precontracted segments and in moderate concentrations it constricted both precontracted and resting segments. When arterial segments from different parts of the pulmonary vascular tree were compared, only small interregional differences in the vasomotor response were seen. 3. Mepyramine caused a parallel shift to the right of the histamine-induced concentration-response curves for both the trachea and the pulmonary artery, indicating a contractile H1-receptor. Cimetidine did not affect the histamine-induced contraction of the trachea, but a shift to the left was evident for low concentrations of histamine in the pulmonary artery. This is consistent with a dilator H2-receptor in the pulmonary artery. The pA2-value for mepyramine in the pulmonary artery, 8.75, was not affected by the presence of cimetidine. Thioperamide, a selective H3 antagonist, shifted the concentration-response for the trachea to the left. Schild analysis for histamine and mepyramine yielded a line with a slope of 0.61, whereas the same analysis in the presence of thioperamide yielded a line with a slope of 1.05 and an approximated pA2-value of 9.57. These results indicate the presence of a relaxant H3 receptor in the trachea. In precontracted tracheal segments, application of mepyramine and cimetidine did not affect the low dose histamine relaxation. Thioperamide caused a parallel shift of the histamine concentration-response curve to the right, supporting the suggestion of a dilator H3-receptor in the trachea. The pA2-value for thioperamide, in the presence of mepyramine, was 7.79. In precontracted pulmonary arteries the histamine-induced dilatation was small. In the presence of mepyramine a rather strong histamine-induced dilatation became evident and this concentration-response curve could be shifted to the right by cimetidine, with a pA2-value of 6.49. This is compatible with a dilator H2-receptor. 4. The H1-receptor agonists, thiazolylethylamine, 2-methylhistamine and pyridylethylamine and the rather unselective H2-agonist, 4-methylhistamine, induced contraction of resting tracheal and pulmonary arterial segments. In precontracted segments of trachea, all H1 and H2 agonists studied induced a dilator response. The two rather unselective histamine receptor agonists 2-methylhistamine and 4-methylhistamine were about 100 times more potent than other H1 and H2 agonists tested. In the pulmonary artery, the H2 agonists, impromidine, dimaprit and 4-methylhistamine induced a concentration-dependent relaxation. The relaxation of the pulmonary artery, elicited by the H1 agonists,thiazolylethylamine and pyridylethylamine, was smaller, but more potent than the response induced by the H2 agonists. This may reflect the presence of a separate dilator H1-receptor.5. R-alpha-methylhistamine induced a three phased response in precontracted tracheal segments. In low concentrations, a concentration-dependent dilator response appeared. At moderate concentrations, a stage with a plateau or a small contraction was seen, followed at high concentrations by a new concentration-dependent relaxation. The first dilator phase was similar to that obtained for histamine in the same preparation.6. Removal of the epithelium or endothelium enhanced the contractile histamine response in both the trachea and the pulmonary artery as well as the dilator response in the trachea. These results support the hypothesis that the endothelial layer may serve as a barrier against the penetration of certain mediators. In the precontracted pulmonary artery, the small initial dilatation was abolished whereas the second dilatation seen in the presence of mepyramine was slightly reduced. This may reflect the influence of two separate histamine receptors, one of which is associated with the release of an endothelium dependent dilator factor or factors.7. In the guinea-pig trachea, histamine-induced contraction is mediated through H1-receptors where as dilatation probably involves an H3-receptor on the smooth muscle. The guinea-pig pulmonary artery appears to be endowed with a contractile H1 receptor on the smooth muscle cells and a dilator H1 receptor located on the endothelium. A dilator H2 receptor on the smooth muscle cells seems, at least in vitro, to be the most potent mediator of histamine-mediated pulmonary arterial dilatation.

Animals↗
PubMed1997

Effect of adenosine and histamine receptor stimulation on canine histamine release to pentagastrin.

The effects of adenosine and histamine 2 and histamine 3 receptor agonists on the regulation of gastric histamine release were examined in anesthetized mixed-breed dogs. All compounds were infused directly into the gastrosplenic artery to avoid perturbations in systemic hemodynamics, and the gastric histamine release was stimulated with pentagastrin. The histamine concentration in plasma samples was measured utilizing gas chromatography-negative-ion chemical ionization mass spectroscopy. Pentagastrin consistently stimulated gastric histamine release with the peak stimulation occurring at 5 min, while neither 30 nor 100 microM of adenosine altered the effect of pentagastrin on histamine release. In addition, theophylline at 20 microg/ml exhibited no effect on stimulated histamine release. The histamine 2 receptor agonist dimaprit, at 1 and 3 microM, attenuated pentagastrin-stimulated histamine release at the 5-min time period, but the difference was not sustained at later time points (histamine release from 1.4 +/- 0.6 to 92 +/- 18 ng/min at 5 min with pentagastrin alone; from 1.2 +/- 0.5 to 32 +/- 11 ng/min with pentagastrin plus 1 microM dimaprit, and from 2.0 +/- 1.1 to 32 +/- 9 ng/min with pentagastrin plus 3 microM dimaprit), while the H2 receptor antagonist cimetidine exhibited no effect on pentagastrin-stimulated histamine release. The histamine 3 receptor agonist (R)-alpha-methylhistamine attenuated the pentagastrin-stimulated histamine release at the 5- and 10-min time periods only at 1 microM without showing any effect at the higher (3 microM) concentration. Thioperamide, a H3 receptor antagonist, did not modify pentagastrin-stimulated histamine release. These data demonstrate that adenosine has no modulatory role on gastric histamine release, but histamine via H2 and H3 histamine receptors could modulate its own release but only to a modest degree as compared with the potent effect of the paracrine hormone somatostatin.

Adenosine↗
PubMed1997

In vitro relaxation of dog cerebral veins in response to histamine is mediated by histamine H2 receptors.

There is little information on the histamine receptor mechanisms involved in cerebral venodilation, thus the role of histamine present in human cerebrospinal fluid is difficult to assess. In isolated canine pial veins, concentration-response curves to histamine (10[-7]-10[-3] M), the histamine H1 receptor agonist, 2-pyridylethylamine (10[-6]-10[-2] M), the histamine H2 receptor agonist, dimaprit (S-(3-dimethylaminopropyl) isothiourea dihydrochloride, 10[-6]-10[-2] M), and the histamine H3 receptor agonist, imetit (S-[2-(1 midazol-4-yl)ethyl]isothiourea dihydrobromide, 10[-7]-10[-3] M) were isometrically determined. In resting veins, histamine, 2-pyridylethylamine and dimaprit had no significant effect, whereas in endothelin-1-precontracted veins, these drugs produced concentration-dependent relaxation (Emax in % of active tone and pD2 were: for histamine, 72 +/- 6 and 5.36 +/- 0.09; for 2-pyridylethylamine, 59 +/- 5 and 3.28 +/- 0.05; for dimaprit, 65 +/- 7 and 4.81 +/- 0.10, respectively). The relaxations in response to histamine and dimaprit were competitively antagonized by the histamine H2 receptor antagonist, cimetidine (3 x 10[-6]-10[-4] M) (pA2 = 6.07 +/- 0.03 for histamine, and 6.09 +/- 0.07 for dimaprit), but were not affected by the histamine H1 receptor antagonist, chlorpheniramine (10[-6] M) or the histamine H3 receptor antagonist, thioperamide (N-cyclohexyl-4-(1-H-imidazol-4-yl)-1-piperidine-carbothioamide maleate, 10[-6] M). The relaxation in response to 2-pyridylethylamine was inhibited by cimetidine (10[-5] M), but not by chlorpheniramine (10[-6] M). Imetit produced a small contraction in resting veins (14 +/- 4 mg) and precontracted veins (20 +/- 3 mg), which was not modified by thioperamide (10[-6] M). The relaxation of veins in response to histamine was not modified by endothelium removal, nor by the inhibitor of nitric oxide synthase, N(G)-nitro-L-arginine methyl ester (10[-4] M), or the cyclooxygenase inhibitor, meclofenamate (10[-5] M). Therefore, in pial veins: (1) histamine produces relaxation by activation of histamine H2 receptors, probably located in the smooth musculature, with no participation of histamine H1 and H3 receptors, and (2) endothelium, nitric oxide and prostanoids are probably not involved in the relaxation in response to histamine.

Animals↗
PubMed2006

Histamine-induced ion secretion across rat distal colon: involvement of histamine H1 and H2 receptors.

The aim of the present study was to investigate the effect of histamine, a product of e.g. mast cells, on short-circuit current (I(sc)) across rat distal colon. Histamine concentration-dependently stimulated an increase in I(sc), which often was preceded by a transient negative current. Neither a release of neurotransmitters nor a release of prostaglandins contributed to the histamine response. The histamine-induced increase in I(sc) was blocked by the histamine H(1) antagonist, pyrilamine, but was resistant against the histamine H(2) antagonist, cimetidine. Conversely, the histamine H(1) agonist, TMPH (2-(3-trifluoromethylphenyl)histamine), exclusively evoked an increase in I(sc), whereas the histamine H(2) agonist, amthamine, evoked only a decrease in I(sc) suggesting that stimulation of different types of histamine receptors is responsible for the two phases of the response evoked by native histamine. Histamine induces the opening of glibenclamide-sensitive Cl(-) channels and of charybdotoxin-sensitive K(+) channels in the apical membrane as demonstrated by experiments at basolaterally depolarized epithelia. A further action site is the basolateral membrane, because histamine stimulates a charybdotoxin- and tetrapentylammonium-sensitive K(+) conductance in this membrane as observed in tissues, in which the apical membrane was permeabilized with an ionophore, nystatin. The increase in I(sc) evoked by histamine was blocked after depletion of intracellular Ca(2+) stores with cyclopiazonic acid and after blockade of inositol 1,4,5-trisphosphate (IP(3)) receptors, suggesting a release of stored Ca(2+). This was confirmed by the observation that the histamine H(1) agonist TMPH induced an increase in the fura-2 ratio signal of epithelial cells within isolated colonic crypts. Consequently, the mediator histamine seems to stimulate both histamine H(1) and H(2) receptors, from which the former seems to be prominently involved in the induction of epithelial chloride secretion.

Animals↗
PubMed1973

Histamine release induced by human leukocyte lysates. Reabsorption of previously released histamine after exposure to cyclic amp-active agents.

The role of cyclic AMP in histamine release induced by human leukocyte lysates was investigated. Leukocytes were incubated with leukocyte lysates prepared by ultrasonic disruption, and histamine was determined fluorimetrically. Several cyclic AMP-active agents had a marked inhibitory effect on histamine release. Theophylline and isoproterenol produced 50% inhibition at concentrations of less than 10(-5) M. Prostaglandin E(1) and dibutyryl cyclic AMP inhibited release by 50% at 7 x 10(-8) M and 6 x 10(-5) M concentrations, respectively. Histamine, which has recently been shown to increase leukocyte cyclic AMP, had a pronounced inhibitory effect on lysate-induced histamine release, producing 50% inhibition at a concentration of only 2.5 x 10(-12) M.Leukocytes, incubated with leukocyte lysates, were sampled at various times and assayed for free histamine released into the incubation mixture supernates, and for bound histamine associated with the leukocyte buttons after centrifugation. Theophylline, prostaglandin E(1) and dibutyryl cyclic AMP not only blocked histamine release, but also caused a progressive decrease in free histamine when added at any time up to 30 min after initiation of the release reaction. As the free histamine decreased after addition of the inhibitors, there was a corresponding increase in the bound histamine, suggesting that previously released histamine was reabsorbed by the leukocytes after exposure to cyclic AMP-active agents. Continued incubation of leukocytes in their own histamine after completion of the release reaction also resulted in reabsorption of the previously released histamine. Previous studies have indicated that cyclic AMP inhibits leukocyte histamine release. The results of the present studies suggest that cyclic AMP modulates histamine release induced by human leukocyte lysates by stimulating reabsorption of histamine from the extracellular environment. These studies also suggest that previously released extracellular histamine may stimulate its own reabsorption by increasing the intracellular level of cyclic AMP.

Absorption↗
PubMed1979

Differentiation of the roles of histamine H1- and H2-receptors in the mediation of the effects of histamine in the isolated working heart of the guinea-pig.

1 Differentiation of the roles of histamine H1- and H2-receptors in the mediation of the effects of histamine on the isolated working heart of the guinea-pig was achieved through the use of histamine and selective histamine receptor agonists and antagonists. 2 Histamine over the dose range 10(-9) mol to 10(-6) mol produced dose-related increases in sinus rate, left intraventricular pressure (LVP)max, LVdP/dtmax, coronary flow, aortic flow, total cardiac output and external pressure-volume work. 3 Dimaprit, a selective histamine H2-receptor agonist, produced very similar responses to histamine. 4 2-Pyridylethylamine, a selective histamine H1-receptor agonist, had little effect on cardiac function unless large doses were administered. Such doses produced increases in all measured parameters. 5 Cimetidine, a selective histamine H2-receptor antagonist, antagonized the effects of histamine and dimaprit and some but not all effects of 2-pyridylethylamine. In the presence of cimetidine a decrease in all parameters with the exception of sinus rate was observed with both histamine and 2-pyridylethylamine. 6 The selective histamine H1-receptor antagonist, mepyramine, had little effect on responses to all three agonists. However, the depressant effects observed with histamine and 2-pyridylethylamine in the presence of cimetidine were antagonized by mepyramine. 7 The results indicate the important role of the histamine H2-receptor in the mediation of the gross cardiac effects of histamine and also indicate that histamine H1-receptors can mediate cardiac depression.

Animals↗
PubMed1998

In vivo modulation of rat hypothalamic histamine release by the histamine H3 receptor ligands, immepip and clobenpropit. Effects of intrahypothalamic and peripheral application.

We investigated the effect of the new potent and selective histamine H3 receptor agonist, immepip, and the histamine H3 receptor antagonist, clobenpropit, on in vivo neuronal histamine release from the anterior hypothalamic area of urethane-anesthetized rats, using microdialysis. Intrahypothalamic perfusion with immepip at concentrations of 1 and 10 nM reduced histamine release to 75% and 35% of its basal level, respectively. Peripheral injection of immepip (5 mg/kg) caused a sustained decrease in histamine release of 50%. Clobenpropit potently increased histamine release after intrahypothalamic perfusion. The maximal increase in histamine release was 2-fold, observed at a concentration of 10 nM clobenpropit. Peripheral injection of clobenpropit (5-15 mg/kg) increased histamine release to about 150% of the basal value. A more marked increase in histamine release was found after injection of the histamine H3 receptor antagonist, thioperamide (5 mg/kg). In conclusion, intrahypothalamic perfusion of the histamine H3 receptor agonist, immepip and the histamine H3 receptor antagonist, clobenpropit, potently and oppositely modulated in vivo histamine release from the anterior hypothalamic area. The decreased histamine release after peripheral injection of immepip indicates that this novel agonist readily crosses the blood-brain barrier, making it a potential candidate for in vivo histamine H3 receptor studies. The differential increase in histamine release after peripheral injection of clobenpropit and thioperamide is discussed.

Animals↗
PubMedDate not supplied

Autoregulation of enterochromaffin-like cell histamine secretion via the histamine 3 receptor subtype.

INTRODUCTION: The neuroendocrine histamine-secreting cell of the gastric fundus, the enferochromaffin-like cell, is the principal regulator of parietal cell acid secretion. We have proposed that histamine may regulate its own synthesis and release via an autocrine mechanism. The purpose of this study was to evaluate the role of the histamine receptor subtypes H1, H2 and H3 in the regulation of this phenomenon. METHODS: Purified ECL cells were isolated by pronase digestion and EDTA exposure of the rat stomach, followed by particle size and density separation using counterflow elutriation and Nycodenz gradient centrifugation, 24-hr cultured cells were pretreated for 30 min with the agents; H1 receptor agonist (2-[(3-trimethyl)-diphenyl] histamine) (TMPH), H1 receptor antagonist (terfenadine); H2 receptor agonist (dimaprit) or antagonist (cimetidine or loxitidine); or H3 receptor agonist (imetit) or antagonist (thioperamide) (all tested, 10(-10)-10(-6) M). Gastrin was then used to stimulate histamine secretion. Histamine secretion was quantified by specific enzyme-immunoassay. RESULTS: Basal histamine secretion was 2.7 +/- 0.14 nmol/10(3) cells. Gastrin-stimulated (10 nM) levels were 4.6 +/- 0.4 nmol/10(3) cells (p < .01). TMPH inhibited both basal and gastrin driven histamine secretion with a maximal effect (34 percent) (1.78 +/- 0.08 nmol/10(3) cells) and an IC50 of > 5 x 10(-7) M. H1 receptor antagonism did not alter histamine secretion alone or in combination with gastrin. Neither H2 receptor stimulation nor antagonism had any effect on histamine secretion alone or in combination with gastrin. Gastrin-induced histamine secretion was dose-dependently inhibited by imetit (H3 agonist) with a maximal effect (2.4 +/- 0.6 nmol/10(3) cells) (p < .05) and an IC50 of 10(-9) M. Conversely, Thioperamide (H3 antagonist) dose-dependently augmented gastrin-stimulated histamine secretion with a maximum effect (5.7 +/- 0.5 nmol/10(3) cells) (p < .05) at 10(-8) M and an EC50 of 7 x 10(-10) M. CONCLUSION: These data are consistent with the presence of an H3 receptor on the ECL cell which modulates gastrin-stimulated histamine secretion. Our observations support the proposal that a histamine-mediated short-loop autocrine regulatory mechanism of ECL cell secretion exists.

Animals↗
PubMed1988

Neutrophils and mast cells. Comparison of neutrophil-derived histamine-releasing activity with other histamine-releasing factors.

Human neutrophil-derived histamine-releasing activity (HRA-N) was partially purified and found to contain a heat-stable 1400 to 2300-Da fraction which caused human basophils and rat basophil leukemia cells (RBL) to degranulate. The capacity of HRA-N to activate basophils was not related to the gender or atopic status of the basophil donor, but was related to anti-IgE responsiveness. Several lines of evidence suggest that HRA-N and anti-IgE induce histamine release through distinctly different mechanisms: 1) the time course of HRA-N- and anti-IgE-induced RBL histamine release are different; 2) HRA-N causes histamine release from RBL with and without surface-bound IgE; 3) lactic acid stripping of IgE from human basophils reduces anti-IgE-induced histamine release, but has no consistent effect on HRA-N-induced histamine release; and 4) passive sensitization of lactic acid-stripped basophils with IgE restores anti-IgE-induced histamine release but not HRA-N-induced histamine release. Several histamine-releasing factors (HRF) were compared with HRA-N. Human nasal HRF (HRF-NW, crude and partially purified fractions of 15 to 30, 3.5 to 9, and less than 3.5 kDa), like HRA-N, caused equal histamine release from both native and IgE-sensitized RBL. However, only the 15- to 30-kDa fraction caused histamine release from human basophils in the doses tested. Mononuclear cell HRF (HRF-M, crude and a partially purified 25 kDa Mr fraction) and platelet HRF (HRF-P, crude preparation) failed to cause histamine release from either native or IgE-sensitized RBL but caused 30 +/- 5.5% and 20 +/- 10% net histamine release from human basophils, respectively. HRA-N and HRF-NW were both stable to boiling. These data, taken together, suggest that the capacity of HRA-N to induce RBL and human basophil histamine release and of HRF-NW to stimulate RBL histamine release is independent of IgE. The data further suggest that HRA-N and HRF-NW can be distinguished by size, and that they both differ from mononuclear cell HRF and platelet HRF. Thus, it appears that inflammatory cells generate a family of distinct HRF.

Animals↗