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Published on: September 18, 2014
Stimulatory effect of (R) alpha-methylhistamine on duodenal HCO3- secretion in anaesthetized rats
G Coruzzi1, E Gambarelli, G Bertaccini
1Istituto di Farmacologia, Università di Parma, Italy.
Abstract:
The effect of the histamine H3 receptor agonist (R) alpha-methylhistamine on duodenal bicarbonate secretion was investigated in the anaesthetized rat. (R) alpha-methylhistamine (3-30 mumol/kg i.v.) caused a dose-dependent increase in alkaline secretion which was completely blocked by the H3 receptor antagonist clobenpropit (3 mumol/kg i.v.). This antagonist caused a slight reduction (19%) of the secretory response to PGE2 50 micrograms/kg i.v. These data indicate that the alkaline response to (R) alpha-methylhistamine is related to the activation of histamine H3 receptors and suggest that this could be an additional mechanism involved in the previously observed gastroprotective effect of this compound.
Insights
The histamine H3 receptor agonist (R) alpha-methylhistamine stimulates duodenal bicarbonate secretion in rats. This effect is mediated by H3 receptors and may contribute to gastroprotection.
Area of Science:
- Gastroenterology
- Pharmacology
- Physiology
Background:
- Histamine H3 receptors play a role in regulating gastrointestinal functions.
- The gastroprotective effects of (R) alpha-methylhistamine have been previously observed.
- Understanding the mechanisms of duodenal bicarbonate secretion is crucial for gastrointestinal health.
Purpose of the Study:
- To investigate the effect of the histamine H3 receptor agonist (R) alpha-methylhistamine on duodenal bicarbonate secretion in rats.
- To determine if the observed effects are mediated through histamine H3 receptors.
- To explore the potential contribution of this mechanism to the gastroprotective properties of (R) alpha-methylhistamine.
Main Methods:
- Administered varying doses of (R) alpha-methylhistamine intravenously to anesthetized rats.
- Utilized the H3 receptor antagonist clobenpropit to block receptor activity.
- Measured duodenal alkaline secretion in response to drug administration.
- Assessed the effect of the antagonist on PGE2-induced secretion.
Main Results:
- (R) alpha-methylhistamine induced a dose-dependent increase in duodenal alkaline secretion.
- The H3 receptor antagonist clobenpropit completely blocked the secretory response to (R) alpha-methylhistamine.
- Clobenpropit slightly reduced the secretory response to PGE2 (19%).
Conclusions:
- The alkaline secretion induced by (R) alpha-methylhistamine is mediated by the activation of histamine H3 receptors.
- Histamine H3 receptor activation represents an additional mechanism contributing to the gastroprotective effects of (R) alpha-methylhistamine.
- These findings provide insights into the pharmacological regulation of duodenal bicarbonate secretion.
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