EVIDENCE THAT HISTAMINE H3 RECEPTORS ARE INVOLVED IN THE CONTROL OF GASTRIC-ACID SECRETION IN THE CONSCIOUS CAT

In an attempt to assess the role of histamine H-3 receptors in the control of gastric acid secretion, the effects of the selective histamine H-3 receptor agonist, (R)-alpha-methylhistamine and antagonist, thioperamide were evaluated in the conscious gastric fistula cat under basal conditions and against different stimuli. (R)-alpha-methylhistamine (0.05 - 0.2-mu-mol/kg/h) was ineffective against spontaneous and dimaprit-induced acid secretion; it also did not reduce significantly pentagastrin-induced acid output, but caused a dose-dependent (0.05 - 0.1-mu-mol/kg/h) and significant inhibition of the acid response to 2-deoxy-D-glucose. Thioperamide (0.02 - 0.04-mu-mol/kg/h) did not modify spontaneous acid secretion, whereas it evoked a significant enhancement of the acid response to submaximal doses (50 mg/kg i.v.) of 2-deoxy-D-glucose. Thioperamide completely reversed the inhibitory effect of (R)-alpha-methylhistamine against 2-deoxy-D-glucose-induced secretion, while leaving unaffected the inhibition induced by somatostatin. These data suggest that histamine H-3 receptors may be involved in the control of acid secretion stimulated by indirectly acting secretagogues.