8-OH-DPAT STIMULATES GASTRIC-ACID SECRETION THROUGH A VAGAL-INDEPENDENT, ADRENAL-MEDIATED MECHANISM

Serotonin (5-hydroxytryptamine, 5-HT) is a neuroendocrine component of the gastrointestinal tract. 5-HT1A receptors exist both in the brain and have been demonstrated autoradiographically in high density in the rat stomach. However, the physiologic role of 5-HT1A receptors in mod ulating gastric function is not known. The effect of the selective 5-H T1A receptor agonist, (+/-)-8-hydroxy-2-(n-dipropylamino)tetralin (8-O H-DPAT), on gastric acid secretory function was compared to 5-HT in ac ute, urethane-anesthetized gastric-fistulated rats during pentagastrin infusion. 5-HT inhibited, but 8-OH-DPAT stimulated, gastric acid secr etion in a dose-dependent manner. Bilateral cervical vagotomy or celia c ganglionectomy did not reverse the effect of 8-OH-DPAT on acid secre tion. However, the enhancement of acid by 8-OH-DPAT was attenuated by acute adrenalectomy or close intra-arterial administration of spiperon e, but not idazoxan. Thus, the data suggest that the selective 5-HT1A receptor agonist 8-OH-DPAT may augment gastric secretory function via an adrenal-dependent mechanism.