The histamine H-3 receptor has been shown to inhibit pentagastrin-induced gastric acid secretion in dogs. Since pentagastrin releases histamine in dogs, we have now assessed whether the effects of H-3-receptor ligands may be indirectly mediated by changes in gastric histamine release. Methods: Pentagastrin infusions (1 or 6 mu g/kg/h), alone or together with the H-3-receptor agonist (R)alpha-methylhistamine (1.2 mu mol/kg/h) or the agonist thioperamide (0.1 mu mol/kg/h), were performed in dogs. One group (anaesthetized) was used for enzyme immunoassays of plasma histamine and, when required, (R)alpha-methylhistamine in the gastrosplenic vein, and another group (non-anaesthetized) for measurement of gastric acid secretion. Results: Histamine levels were increased five- and eight-fold after 1 and 6 mu g/kg/h pentagastrin, respectively, whereas acid output was nearly maximal at the lower dosage. (R)alpha-methylhistamine, at a plasma concentration of 0.15 mu M, inhibited histamine release by 78% (P < 0.007) and 37% (not significant) and the total acid output by 44% (P < 0.05) and 19% (not significant) after infusion of 1 and 6 mu g/kg/h pentagastrin, respectively. Thioperamide, together with pentagastrin in low dose, significantly increased histamine 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 pentagastrin in low dosage. The control of acid secretion by the H-3 receptor seems to involve modulation of endogenous histamine release, possibly by means of enterochromaffin-like cells.
|Autori:||Soldani G; Garbarg M; Intorre L; Bertini S; Rouleau A; Schwartz JC|
|Titolo:||Modulation of pentagastrin-induced histamine release by histamine H-3 receptors in the dog|
|Anno del prodotto:||1996|
|Digital Object Identifier (DOI):||10.3109/00365529609009141|
|Appare nelle tipologie:||1.1 Articolo in rivista|