R‐α‐methylhistamine‐induced inhibition of gastric acid secretion in pylorus‐ligated rats via central histamine H₃ receptors

Abstract

1 The effect of central H3 histamine receptor activation on gastric acid and pepsin production has been investigated in pylorus-ligated rats. 2 Intracerebroventricular injections (i.c.v.) of the selective H3 agonist, R-ac-methylhistamine (0.5-50 nmol per rat) caused a dose-dependent inhibition of gastric acid secretion while intravenous administration (5-500 nmol per rat) was completely ineffective. 3 I.c.v. microinjections of mepyramine, tiotidine and thioperamide (51 nmol per rat), selective antagonists at H1-, H2-and H3-sites respectively, failed to modify the acid secretory response to pylorus ligation. 4 The antisecretory effect of R-a-methylhistamine (5 nmol per rat, i.c.v.) was selectively prevented by the H3-blocker, thioperamide (51 nmol per rat, i.c.v.), mepyramine and tiotidine pretreatment being completely inactive. 5 Unlike acid secretion, pepsin production was not significantly affected by all the tested compounds. 6 These findings provide the first pharmacological evidence that the activation of central H3 histamine receptors exerts a negative control in the regulation of gastric acid secretion in conscious pylorus-ligated rats.

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

“…This is the rst in vivo evidence which supports previous in vitro data indicating that gastric H 3 sites act as heteroreceptors in the attenuation of acetylcholine release from electrically stimulated vagus nerve in rats (11). Our nding seems to diverge from previous papers describing the inability of RMH to inhibit rat gastric acid secretion induced by 2-deoxy-D-glucose or by pylorusligation (16,17). Actually, this discrepancy could be primarily due to the different experimental conditions adopted.…”

“…Indeed, RMH does not affect basal or pharmacologically stimulated H ‡ production in rat isolated gastric fundus (16) and minimally increases basal acid secretion in isolated vascularly perfused rat stomach (10). Furthermore, after peripheral ORIGINAL ARTICLE administration, this H 3 agonist fails to modify acid secretion in pylorus-ligated rats while, but only at high doses, it causes an increase in basal and pharmacologically stimulated acid output in lumen-perfused stomach of anaesthetized rats (16,17). In our attempt to further investigate the extent to which the histamine H 3 -receptor subtype is involved in the regulation of gastric acid secretion in rats, we examined the effects produced by H 3 agonist/antagonist challenge on basal acid output and hypersecretion induced by vagal electrical stimulation or by the secretagogues betanechol and pentagastrin in anaesthetized rats.…”

Lack of evidence for histamine H 3 receptor function in rat ileum and human colon

“…Activation of H 3 receptors by peripheral administration of H 3 agonists in cats, dogs and rabbits inhibits gastric acid secretion induced by a number of secretagogues (Bertaccini and Coruzzi 1995), however this effect was not observed in the rat (Barocelli et al 1995).…”

New pharmacological agents for the treatment of gastro‐oesophageal reflux disease

“…There is some evidence that (R)‐alpha‐methylhistamine may provide acid blockade in animal models. For example, intracerebroventricular administration in rats (0.5–50 nmol per rat) induced a dose‐dependent inhibition of acid secretion; however, intravenous administration in this model had no effect 75 . Further evidence of an acid inhibitory effect of H 3 agonists has been provided by dog studies, where dose‐dependent inhibition of pentagastrin‐stimulated acid output has been observed.…”