Different Role of the Histamine H 3 -Receptor in Vagal-, Betanechol-, Pentagastrin-induced Gastric Acid Secretion in Anaesthetized Rats

Abstract

Background : To date, involvement of the histamine H 3 -receptor in the control of gastric acid secretion in rats is not conclusively defined because of the variability of experimental results. This study was therefore aimed at investigating the role of H 3 -receptors in acid secretion produced by nervous or pharmacological stimulation in anaesthetized rats. Methods : Gastric acid output was measured by flushing the rat stomach lumen with 5 ml saline and titrating the flushed perfusate. Hypersecretory responses were evoked through direct vagal stimulation (0.5 msec, 10 Hz, 50 V for 30 min every 30 min) or by stimulation with pentagastrin (20, 40, 100, 250 μg/kg/h i.v.) or betanechol (100, 250, 500 μg/kg/h i.v.). The selective H 3 ligands (R)- α -methylhistamine and thioperamide (100 μg/kg i.v.) were tested alone or in combination on both basal and electrically/pharmacologically induced secretion. Results : Vagally-induced response was significantly reduced by the agonist R- α -methylhistamine and this effect was antagonized by the antagonist thioperamide at a dose unable by itself to modify vagal response. Thioperamide significantly increased acid response only on pentagastrin low dose (20 μg/kg/h) and this effect was counteracted by R- α methylhistamine, which was ineffective when administered alone. Betanechol-induced hypersecretion was substantially unaffected by the H 3 ligands, which were also inactive on basal acid output. Conclusions : Although this functional study confirms the presence of histamine H 3 -receptors in the rat stomach, they appear to have minor weight in regulation of the acid secretion in this species.

• Betanechol
• Gastric Acid Secretion
• Histamine
• Pentagastrin
• Vagal Stimulation