Effect of gastric stimulants on histamine release and circulatory responses (original) (raw)
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British Journal of Pharmacology, 1989
In the isolated vascularly-perfused stomach of the rat, gastrin 1-17 (520pmollP) increased acid output from basal values of 13.7 + 2.7 to 92.5 + 11.4 ymol h1 and venous histamine output from 10.1 + 2.3 to 54.7 + 7.9 nmol h1 (mean + s.e.mean). 2 The H1 receptor agonist 2-methylhistamine (10 pmol l-) increased acid output to 21.6 + 2.9.umolh-' (P <0.05) and reduced basal histamine output to 4.0 + 0.8nmolh-' (P < 0.05). Gastrin-stimulated acid secretion and vascular histamine output was not significantly affected by 2-methylhistamine (10 ymol-1). 3 The H2 receptor agonist, impromidine, dose-dependently increased basal acid secretion, reaching a maximal value of 145.5 + 11.7 pmol h-1 with impromidine (10,umol I'), and maximal gastrin-stimulated acid secretion to 167.4 + 15.1 pmolh-1 with impromidine (IOpmolI-). Impromidine dose-dependently inhibited basal and gastrin-stimulated vascular histamine output. 4 The H3 receptor agonist R-a-methylhistamine, (1 and 10moll'P) minimally increased basal acid secretion. R-a-methylhistamine (10pmoll-1) did not significantly affect maximal gastrinstimulated acid secretion. Basal and gastrin-stimulated vascular histamine outputs decreased to 4.0 + 0.8 (P < 0.05) and 24.7 + 4.7 nmol h1-(P = 0.05) with R-a-methylhistamine (10pmol 1-p). 5 The H2 receptor antagonist ranitidine (2 pmol I1-) did not inhibit basal acid secretion, but acid outputs with gastrin and all histamine agonists were reduced. Ranitidine did not affect histamine release in the basal state, with gastrin or with any histamine agonist tested. 6 We conclude that gastric histamine release in the rat is regulated via a histamine H2 receptor sensitive to the histamine agonists tested, but not to ranitidine. It is unlikely that the inhibition of histamine release is secondary to increased gastric acidity.
Naunyn- …, 1994
The involvement of histamine H 3 receptors in the regulation of gastric acid secretion was investigated in the conscious dog with gastric fistula, by the use of the selective agonist (R)a-methylhistamine and the selective antagonist thioperamide. (R)a-methylhistamine (0.3-1.2 ~tmol/kg/h) induced a dose-related inhibition of the acid secretion induced by pentagastrin and by bombesin, maximum inhibition not exceeding 60-65°70. The inhibitory effect of the H 3 agonist (0.6 ~tmol/kg/h) was inhibitited by thioperamide (0,1 gmol/kg/h), suggesting that the effect was entirely mediated by H 3 receptors. Thioperamide was also able to enhance the acid response to submaximal doses of pentagastrin and bombesin. The acid secretion induced by histamine was not modified by (R)a-methylhistamine (0.3-1.2 gmol/kg/h) but it was significantly enhanced by thioperamide (0.1gmol/kg/h). Neither (R)a-methylhistamine nor thioperamide significantly modified the increase in plasma gastrin levels induced by bombesin. In conclusion these data demonstrate that histamine H3 receptors may represent an effective mechanism for the negative control of stimulated gastric acid secretion in the dog; however, since the inhibition was mainly evident against stimuli which involve the release of histamine, a location of H~ receptors in paracrine cells of the gastric mucosa rather than in gastrin producing cells or parietal cells seems more likely.
Inflammation Research, 2010
Introduction Histamine is not only a potent stimulator of gastric acid secretion, but it also plays a central role in gastroduodenal ulcerogenesis. In the present study we tested the effect of pre-treatment with exogenous prostaglandin E 2 (PGE 2 ) in a new rat model of experimental gastric ulcers induced by combination of histamine and gastric ischemia. Methods In male Wistar rats, a chronic ischemia of gastric mucosa was induced via the clamping of the left gastric artery and vein (L-AV) in combination with pylorus ligation. The following treatment groups of rats (6 rats/group) were investigated: 1) histamine alone (40 mg/kg twice s.c.); 2) vehicle (saline) followed 30 min later by gastric mucosal L-AV ischemia and pylorus ligation combined with histamine (40 mg/kg twice s.c.) and 3) PGE 2 (5 lg/kg i.g.) followed 30 min later by gastric mucosal L-AV ischemia combined with histamine (40 mg/kg twice s.c.) and pylorus ligation. At 4 hr after the clamping of L-AV and pylorus ligation, the area of gastric lesions and gastric acid secretion was determined. Results Histamine treatment failed to produce gastric lesions, but when it was combined with ischemia, the widespread gastric lesions in the corpus mucosa, but not in the antrum, were observed. This damaging effect and decrease in the GBF were significantly attenuated by pretreatment with PGE 2 .
Histamine in the control of gastric acid secretion: a topic review
Pharmacological Research, 2003
In this paper, the current knowledge about the role of histamine in the control of gastric acid secretion is reviewed. In particular, we focus this topic into three sections considering the recent insights on: histamine receptor subtypes involved in gastric acid secretion, the interplay between neuronal-hormonal-paracrine pathways and the cerebral histaminergic control of gastric secretion. From the careful perusal of scientific literature, the fundamental role of histamine as local stimulator of gastric acid secretion via H 2 receptors is fairly confirmed while for the H 3 receptor only a minor modulating role is hypothesized. An undisputed function of ECL cells as controllable source of histamine within the so-called gastrin-ECL cell-parietal cell axis is generally proposed and the intriguing possibility of a remote control of gastric secretion via H 3 receptors is also suggested.
Effects of pentagastrin on intestinal absorption and blood flow in the anaesthetized dog
The Journal of Physiology, 1980
/tg/min) was infused i.v. into fed and fasted anaesthetized dogs and the intestinal absorption of NaCl and H20 and blood flow were determined. The influence of pentagastrin-induced cardiovascular changes on absorption was investigated. 2. 22Na and 3H20 were used to determine the unidirectional Na and H20 fluxes from saline perfused through the ileal lumen and the clearances of 3H20 were used to calculate total and absorptive site blood flow. 3. Ileal absorption of Na and H20 was reduced by 10 tg/min pentagastrin due primarily to significant increases in the secretary flux of Na and decreases in the absorptive flux of H20 in both fed and fasted animals. 4. Neither total intestinal blood flow, arterial nor mesenteric vein pressure were changed by pentagastrin but absorptive site blood flow was decreased in fasted but not in fed dogs. 5. Pretreatment with atropine reduced the effects of pentagastrin but pretreatment with guanethidine potentiated the effects of pentagastrin. 6. Absorptive site blood flow was positively linearly correlated with the absorptive fluxes of both Na and H20. The relationships between the secretary fluxes of Na and H20 and estimated capillary pressure were changed from a positive relationship in control periods to a less positive or negative relationship following pentagastrin. 7. It was concluded that pentagastrin reduces intestinal absorption through both a cardiovascular effect and an effect on the intestinal epithelium. Also, there is a strong autonomic component in the effects of pentagastrin on intestinal absorption.
A study of the role of histamine in gastric secretion in the isolated guinea pig gastric preparation
Agents and Actions, 1992
Mast cell histamine could be involved in the regulation of gastric acid secretion. In order to compare the results on mast cell histamine obtained in experiments carried out on the isolated mouse stomach to guinea pig stomach, the method for isolated mouse stomach was adapted to isolated stomach wall of the guinea pig. The modified preparation gave repeatable secretory responses to histamine and carbachol, similar to those in the isolated mouse stomach. Compound 48/80 (100 lag/ml) did not evoke secretion, whereas a calcium ionophore, chlortetracycline (CTC), reduced basal secretion, as did low concentrations (< 100 nmol/1) of histamine; chloropyramine (100 lamol/1) counteracted the inhibitory effect of histamine. Histological examination of the guinea pig gastric mucosa showed more connective tissue mast cells (CTMC) than mucosal mast cells (MMC). CTMC were degranulated in response to chlortetracycline but not to compound 48/80.
Agents and Actions, 1977
The effect of cyclic somatostatin on pentagastrin-and histamine-stimulated gastric acid secretion in conscious cats was studied. Evidence is produced that somatostatin competitively inhibits pentagastrin-stimulated gastric acid secretion whereas it inhibits histamine-stimulated secretion by a mechanism which is not competitive in nature. The vagus nerves seem to be involved in the mode of action of somatostatin as the inhibitory effects are greater in vagotomized than in vagus intact animals.
Gastric antisecretory effects of compound BP 2-94: a histamine H3-receptor agonist prodrug
Digestive diseases and sciences, 1999
Compound BP 2-94 is an orally available prodrug of the histamine H3-receptor agonist (R)-alpha-methylhistamine, which was found to produce higher plasma levels than the parent drug in humans. In the present study radioimmunoassay was carried out in dogs to investigate the generation of (R)-alpha-methylhistamine in vivo after intragastric administration of the prodrug. The effects of BP 2-94 on gastric acid secretion and on histamine, gastrin, and somatostatin release were also investigated. After intragastric administration of BP 2-94 (10 mg/kg), both the prodrug and (R)-alpha-methylhistamine were detected in plasma: plasma levels of (R)-alpha-methylhistamine decayed with a T1/2 of about 1 hr and displayed concentrations as high as 50-fold the EC50 of the drug at the H3 receptor for at least 2 hr. In conscious dogs provided with gastric fistula BP 2-94, administered at 10 and 30 mg/kg intragastrically, caused a dose-dependent inhibition (maximum reduction was about 80%) of the acid ...