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 modulating gastric function is not known. The effect of the selective 5-HT1A receptor agonist, (+/-)-8-hydroxy-2-(n-dipropylamino)tetralin (8-OH-DPAT), on gastric acid secretory function was compared to 5-HT in acute, urethane-anesthetized gastric-fistulated rats during pentagastrin infusion. 5-HT inhibited, but 8-OH-DPAT stimulated, gastric acid secretion in a dose-dependent manner. Bilateral cervical vagotomy or celiac ganglionectomy did not reverse the effect of 8-OH-DPAT on acid secretion. However, the enhancement of acid by 8-OH-DPAT was attenuated by acute adrenalectomy or close intra-arterial administration of spiperone, 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.
Department of Pharmacology, Dokuz Eylul University, Izmir, Turkey.
S
S
Gidener
K J
KJ
LePard
R L
RL
Stephens
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology*; D000311:Adrenal Glands / Q000502:physiology*; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D004146:Dioxanes / Q000494:pharmacology; D018492:Dopamine Antagonists / Q000494:pharmacology; D005728:Ganglia, Sympathetic / Q000187:drug effects / Q000502:physiology; D005744:Gastric Acid / Q000378:metabolism*; D005745:Gastric Acidity Determination; D019329:Idazoxan; D007093:Imidazoles / Q000494:pharmacology; D008297:Male; D009271:Naltrexone / Q000031:analogs & derivatives / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*; D013134:Spiperone / Q000494:pharmacology; D013157:Splenic Artery / Q000502:physiology; D013268:Stimulation, Chemical; D014628:Vagotomy; D014630:Vagus Nerve / Q000502:physiology*
D000317:Adrenergic alpha-Antagonists; D004146:Dioxanes; D018492:Dopamine Antagonists; D007093:Imidazoles; D017366:Serotonin Receptor Agonists; C051844:norbinaltorphimine; D013134:Spiperone; D009271:Naltrexone; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D019329:Idazoxan