The effect of beta andrenoceptor stimulation of canine stomach on pentagastrin-stimulated histamine release.
The effect of beta adrenergic agonist isoproterenol, infused directly into the gastrosplenic artery in anesthetized mixed-breed dogs, on pentagastrin-stimulated gastric histamine release was examined to clarify the potential mechanisms by which beta adrenoceptor stimulation results in gastric acid inhibition. Two doses of isoproterenol (3 and 10 ng/kg/min) were infused with pentagastrin; histamine and n(tau)-methyl-histamine concentrations were measured in arterial and gastric venous samples, and their gastric secretory rates were calculated. Both doses of isoproterenol decreased histamine-secretory rate to pentagastrin from a peak of 234 +/- 51.5 ng/min with vehicle to 17.7 +/- 4.2 ng/min with the 3 ng/kg/min dose of isoproterenol and to 8.6 +/- 2.9 ng/min with the 10 nk/kg/min dose of isoproterenol. The change in N(tau)-methyl-histamine-secretory rate paralleled the histamine-secretory rate. Concomitantly with the histamine-secretory rate, the effect of beta adrenoceptor agonist on gastric somatostatin secretion was also examined. The lower dose of isoproterenol stimulated somatostatin-secretory rate from 4.0 +/- 1.8 to 31.8 +/- 10.3 ng/min, and the higher dose of isoproterenol increased somatostatin-secretory rate from 6.0 +/- 3.1 to 61.5 +/- 21.5 ng/min, whereas isoproterenol potentiated pentagastrin-stimulated gastric somatostatin release. These data demonstrate that isoproterenol is a potent inhibitor of pentagastrin-stimulated gastric histamine release, and the mechanism may be related to the concomitant somatostatin release. Thus, the most likely mechanism by which beta adrenoceptor stimulation results in inhibition of gastric acid secretion is through down-regulation of gastric histamine release.
Payne
N A
NA
Department of Medicine, University of Colorado Health Sciences Center, Denver, USA.
Gerber
J G
JG
D000818:Animals; D001783:Blood Flow Velocity / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D004285:Dogs; D005260:Female; D006636:Histamine Release / Q000187:drug effects*; D007545:Isoproterenol / Q000494:pharmacology*; D008297:Male; D010418:Pentagastrin / Q000494:pharmacology*; D013270:Stomach / Q000187:drug effects*; D013997:Time Factors
D010418:Pentagastrin; D007545:Isoproterenol