Inhibitory alpha 2-adrenergic mechanism regulating gastric secretion in pylorus-ligated rats

Several alpha-adrenoceptor agonists given intracerebroventricularly or subcutaneously to rats were assessed for their effects on gastric secretion under condition of pylorus ligation. Intracerebroventricular injection of alpha-adrenoceptor agonists reduced gastric secretion, in the following order (relative potency, clonidine = 1): oxymetazoline (100) greater than clonidine (1) greater than methoxamine (0.024) greater than phenylephrine (0.003). The antisecretory effects of oxymetazoline and clonidine given intracerebroventricularly were antagonized with yohimbine administered by the same route. Subcutaneous injection of alpha-adrenoceptor agonists also reduced gastric secretion, in the following order (relative potency, clonidine = 1): clonidine (1) greater than oxymetazoline (0.3), much greater than phenylephrine (0.001) approximately methoxamine (0.0006). Oxymetazoline, when given intracerebroventricularly, was most effective in decreasing the volume and titratable acidity of gastric secretion. Pretreatment with 6-hydroxydopamine intracerebroventricularly (250 micrograms/rat x 2; 72 and 120 h before) reduced the antisecretory effect of clonidine given intracerebroventricularly. Thus, gastric secretion appears to be regulated in an inhibitory manner by alpha 2-, but not by alpha 1- adrenoceptors in the central and peripheral nervous systems, in pylorus-ligated rats.