Histamine release in the isolated vascularly perfused stomach of the rat: regulation by autoreceptors.

1. In the isolated vascularly-perfused stomach of the rat, gastrin 1-17 (520 pmol 1(-1)) increased acid output from basal values of 13.7 +/- 2.7 to 92.5 +/- 11.4 mumol h-1 and venous histamine output from 10.1 +/- 2.3 to 54.7 +/- 7.9 nmol h-1 (mean +/- s.e.mean). 2. The H1 receptor agonist 2-methylhistamine (10 mumol 1(-1)) increased acid output to 21.6 +/- 2.9 mumol h-1 (P less than 0.05) and reduced basal histamine output to 4.0 +/- 0.8 nmol h-1 (P less than 0.05). Gastrin-stimulated acid secretion and vascular histamine output was not significantly affected by 2-methylhistamine (10 mumol 1(-1)). 3. The H2 receptor agonist, impromidine, dose-dependently increased basal acid secretion, reaching a maximal value of 145.5 +/- 11.7 mumol h-1 with impromidine (10 mumol 1(-1)), and maximal gastrin-stimulated acid secretion to 167.4 +/- 15.1 mumol h-1 with impromidine (10 mumol 1(-1)). Impromidine dose-dependently inhibited basal and gastrin-stimulated vascular histamine output. 4. The H3 receptor agonist R-a-methylhistamine, (1 and 10 mumol 1(-1)) minimally increased basal acid secretion. R-a-methylhistamine (10 mumol 1(-1)) did not significantly affect maximal gastrin-stimulated acid secretion. Basal and gastrin-stimulated vascular histamine outputs decreased to 4.0 +/- 0.8 (P less than 0.05) and 24.7 +/- 4.7 nmol h-1 (P = 0.05) with R-a-methylhistamine (10 mumol 1(-1)). 5. The H2 receptor antagonist ranitidine (2 mumol 1(-1)) did not inhibit basal acid secretion, but acid outputs with gastrin and all histamine agonists were reduced.(ABSTRACT TRUNCATED AT 250 WORDS)