The effects of alpha-2 agonists and antagonists on gastric acid secretion.

The effects of alpha-2 agonists clonidine, xylazine and guanabenz as well as those of alpha-2 antagonists tolazoline and yohimbine on gastric acid secretion were investigated in Shay rats, Schild rats and isolated guinea-pig gastric fundus. In Shay rats clonidine, xylazine and guanabenz displayed marked antisecretory effects, whereas tolazoline and yohimbine had no effect. Under the same conditions, yohimbine fully prevented the actions of clonidine, xylazine and guanabenz, while tolazoline showed partial antagonism. In Schild rats both clonidine and xylazine displayed a stimulant secretory action, but guanabenz was without effect; cimetidine fully prevented the excitatory effects of clonidine and xylazine. Both tolazoline and yohimbine increased gastric acid secretion in Schild rats: the effect of tolazoline was inhibited by cimetidine, while the effect of yohimbine was prevented by pirenzepine or vagotomy. On isolated guinea-pig gastric fundus, clonidine, xylazine and tolazoline exerted a stimulatory activity, whereas guanabenz and yohimbine had no effect: these excitatory responses were fully prevented by cimetidine. Overall results indicate that clonidine and xylazine have both inhibitory and excitatory effects on gastric acid secretion, while guanabenz produces only inhibitory effects. The inhibitory activity appears to be mediated by activation of presynaptic alpha-2 receptors on the vagus nerve, whereas the excitatory effects seem to be mediated by histaminergic pathway. The stimulant secretory action of tolazoline may be due to its imidazoline-like structure allowing interaction with histamine H2-receptors: accordingly, this effect is lacking for guanabenz, which is structurally unrelated to imidazoline. The excitatory effect of yohimbine appears to be exerted on central cholinergic sites, as indicated by its disappearance in vagotomized rats.