Evidence for central and peripheral serotonergic control of corticosterone secretion in the conscious rat.
Serotonin (5-HT) and 5-HT agonists act on multiple 5-HT receptor subtypes to increase corticosterone secretion. The present experiments describe the effects of a highly selective 5-HT2 receptor agonist DOI [(+-)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane HCl] on plasma corticosterone in conscious, unrestrained, male rats with indwelling arterial and venous catheters. DOI (500 micrograms/kg, i.v.) increased plasma corticosterone levels 6- to 7-fold from 15 to 60 min. Pretreatment with the central 5-HT2 antagonist LY 53857 (100 micrograms/kg, i.v.) blocked the effect of DOI on corticosterone secretion at all times. The peripheral 5-HT2 antagonist xylamidine (100 micrograms/kg, i.v.) attenuated the corticosterone response elicited 15 min after DOI but did not alter the 60-min response. In contrast, dexamethasone pretreatment (350 micrograms/kg, s.c.) attenuated the corticosterone response to DOI at 15 min, but abolished the response at 60 min. The increase in corticosterone levels elicited 5 min after the nonselective 5-HT agonist quipazine (3 mg/kg, i.v.) was also reduced by xylamidine. These data suggest that 5-HT2 receptor agonists increase corticosterone secretion initially, in part, through a direct adrenal mechanism not entirely dependent on adrenocorticotropin, and at later times via a central, dexamethasone-suppressible mechanism. This raises the possibility that endogenous 5-HT in the adrenal medulla may act as a local paracrine to participate in the regulation of corticosterone secretion from the adrenal cortex.
Alper
R H
RH
Department of Pharmacology, Toxicology and Therapeutics, University of Kansas Medical Center, Kansas City.
D000578:Amidines / Q000494:pharmacology; D000662:Amphetamines / Q000037:antagonists & inhibitors / Q000494:pharmacology; D000818:Animals; D003345:Corticosterone / Q000378:metabolism*; D003907:Dexamethasone / Q000494:pharmacology; D004873:Ergolines / Q000494:pharmacology; D008297:Male; D011814:Quipazine / Q000037:antagonists & inhibitors; D051381:Rats; D011919:Rats, Inbred Strains; D011985:Receptors, Serotonin / Q000187:drug effects / Q000502:physiology*; D012702:Serotonin Antagonists / Q000494:pharmacology
D000578:Amidines; D000662:Amphetamines; D004873:Ergolines; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D011814:Quipazine; D003907:Dexamethasone; C032663:LY 53857; C005894:xylamidine; C015952:4-iodo-2,5-dimethoxyphenylisopropylamine; D003345:Corticosterone