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

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Abstract
1 In the isolated vascularly-perfused stomach of the rat, gastrin 1–17 (520 pmol l−1) increased acid output from basal values of 13.7 ± 2.7 to 92.5 ± 11.4 μmol 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 μmol l−1) increased acid output to 21.6 ± 2.9 μmol h−1 (P < 0.05) and reduced basal histamine output to 4.0 ± 0.8 nmol h−1 (P < 0.05). Gastrin-stimulated acid secretion and vascular histamine output was not significantly affected by 2-methylhistamine (10 μmol l−1). 3 The H2 receptor agonist, impromidine, dose-dependently increased basal acid secretion, reaching a maximal value of 145.5 ± 11.7 μmol h−1 with impromidine (10 μmol l−1), and maximal gastrin-stimulated acid secretion to 167.4 ± 15.1 μmol h−1 with impromidine (10 μmol l−1). Impromidine dose-dependently inhibited basal and gastrin-stimulated vascular histamine output. 4 The H3 receptor agonist R-a-methylhistamine, (1 and 10 μmol l−1) minimally increased basal acid secretion. R-a-methylhistamine (10 μmol l−1) did not significantly affect maximal gastrinstimulated acid secretion. Basal and gastrin-stimulated vascular histamine outputs decreased to 4.0 ± 0.8 (P < 0.05) and 24.7 ± 4.7 nmol h−1 (P = 0.05) with R-a-methylhistamine (10 μmol 1−1). 5 The H2 receptor antagonist ranitidine (2 μmol l−1) did not inhibit basal acid secretion, but acid outputs with gastrin and all histamine agonists were reduced. Ranitidine did not affect histamine release in the basal state, with gastrin or with any histamine agonist tested. 6 We conclude that gastric histamine release in the rat is regulated via a histamine H2 receptor sensitive to the histamine agonists tested, but not to ranitidine. It is unlikely that the inhibition of histamine release is secondary to increased gastric acidity.