Different role of the histamine H3-receptor in vagal-, betanechol-, pentagastrin-induced gastric acid secretion in anaesthetized rats.
BACKGROUND
To date, involvement of the histamine H3-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 H3-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 microg/kg/h i.v.) or betanechol (100, 250, 500 microg/kg/h i.v.). The selective H3 ligands (R)-alpha-methylhistamine and thioperamide (100 microg/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-alpha-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 microg/kg/h) and this effect was counteracted by R-alpha-methylhistamine, which was ineffective when administered alone. Betanechol-induced hypersecretion was substantially unaffected by the H3 ligands, which were also inactive on basal acid output.


CONCLUSIONS
Although this functional study confirms the presence of histamine H3-receptors in the rat stomach, they appear to have minor weight in regulation of the acid secretion in this species.
Dip Scienze Farmacologiche Biologiche & Chimiche Applicate, Università di Parma, Italy.
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Ballabeni
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Calcina
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Bosetti
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Chiavarini
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Bertoni
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Impicciatore
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Barocelli
D000818:Animals; D018723:Bethanechol / Q000494:pharmacology*; D005744:Gastric Acid / Q000378:metabolism*; D005753:Gastric Mucosa / Q000502:physiology*; D008297:Male; D023421:Models, Animal; D010277:Parasympathomimetics / Q000494:pharmacology*; D010418:Pentagastrin / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D018100:Receptors, Histamine H3 / Q000502:physiology*; D013270:Stomach / Q000187:drug effects*; D014630:Vagus Nerve / Q000502:physiology*
D010277:Parasympathomimetics; D018100:Receptors, Histamine H3; D018723:Bethanechol; D010418:Pentagastrin