MODULATION OF PENTAGASTRIN-INDUCED HISTAMINE-RELEASE BY HISTAMINE H-3RECEPTORS IN THE DOG

The histamine H-3 receptor has been shown to inhibit pentagastrin-indu ced gastric acid secretion in dogs. Since pentagastrin releases histam ine in dogs, we have now assessed whether the effects of H-3-receptor ligands may be indirectly mediated by changes in gastric histamine rel ease. Methods: Pentagastrin infusions (1 or 6 mu g/kg/h), alone or tog ether with the H-3-receptor agonist (R)alpha-methylhistamine (1.2 mu m ol/kg/h) or the agonist thioperamide (0.1 mu mol/kg/h), were performed in dogs. One group (anaesthetized) was used for enzyme immunoassays o f plasma histamine and, when required, (R)alpha-methylhistamine in the gastrosplenic vein, and another group (non-anaesthetized) for measure ment of gastric acid secretion. Results: Histamine levels were increas ed five- and eight-fold after 1 and 6 mu g/kg/h pentagastrin, respecti vely, whereas acid output was nearly maximal at the lower dosage. (R)a lpha-methylhistamine, at a plasma concentration of 0.15 mu M, inhibite d histamine release by 78% (P < 0.007) and 37% (not significant) and t he total acid output by 44% (P < 0.05) and 19% (not significant) after infusion of 1 and 6 mu g/kg/h pentagastrin, respectively. Thioperamid e, together with pentagastrin in low dose, significantly increased his tamine release by 212% (P < 0.05), whereas acid output increased by 34 % (not significant). Conclusions: The histamine H-3 receptor mediates a negative feedback control of pentagastrin-induced release of gastric histamine. It is tonically activated by endogenous histamine after pe ntagastrin in low dosage. The control of acid secretion by the H-3 rec eptor seems to involve modulation of endogenous histamine release, pos sibly by means of enterochromaffin-like cells.