GASTRIC SECRETORY RESPONSES TO DRUGS AFFECTING ADRENERGIC MECHANISMS IN RATS

¹ Research Laboratories, Parke, Davis & Company, Ann Arbor, Michigan

A series of drugs with either vasoactive or adrenergic properties was evaluated for effects on gastric secretion in pylorus-ligated rats. Peripheral vasoconstrictor or vasodilator drugs do not produce a consistent effect on secretion Whereas vasoconstrictors like norepinephrine, epinephrine and vasopressin were antisecretory, angiotensin and dl-dopa had no effect. Of the vasodilator series, isoproterenol, but not bradykinin, was antisecretory. The majority of chemicals that possess adrenergic blocking properties were weakly antisecretory. Chemicals which prevent uptake of catecholamines were antisecretory and were more potent than those that prevent release of catecholamines. Sympathomimetic amines with indirect or mixed actions showed little effect on secretion, as did chemicals that inhibit catecholamine metabolism. Compounds that interfere with catecholamine synthesis by inhibiting either dopamine--hydroxylase or decarboxylase enzymes had essentially no effect on gastric secretion. Drugs which act on ganglionic or cholinergic sites, e.g., dibutadiamin and atropine, were included for comparison with drugs acting on adrenergic sites. The pharmacologic analysis in this study indicates that catecholamines exert a gastric antisecretory effect in the rat which is independent of vasoactive properties. In general, drugs that increase the biologic half-life of catecholamines decreased gastric secretion.