Effect of selective serotonin agonists on basal, corticotrophin-releasing hormone- and vasopressin-induced ACTH release in vitro from rat pituitary cells.
The present study was undertaken to evaluate the serotonin (5-HT) receptor subtype(s) by which 5-HT acts on the pituitary to stimulate ACTH secretion. We tested the effects of the 5-HT1A receptor agonist 8-hydroxy-2-(di-n-propylamino)-tetralin (8-OH-DPAT), the 5-HT1C receptor agonist metachloro-phenylpiperazine (m-CPP), which also binds to other 5-HT receptors with lower affinity, and the 5-HT2/1C receptor agonist 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) on basal, corticotrophin-releasing hormone (CRH) and arginine vasopressin (AVP)-stimulated ACTH release from primary rat anterior pituitary cell cultures. 5-HT, 8-OH-DPAT and DOI significantly increased basal ACTH release, an effect which was antagonized by 5-HT receptor antagonists. 5-HT and DOI were effective at nanomolar concentrations whereas 8-OH-DPAT was effective at higher concentrations. 5-HT, 8-OH-DPAT (both at 10 nmol/l) and DOI (at higher concentrations) blunted the stimulatory effect of CRH. The suppressive effects of 8-OH-DPAT and DOI on CRH-stimulated ACTH release were antagonized by (-)propranolol, a beta-adrenergic receptor antagonist which binds the 5-HT1A receptor with elevated affinity, and ketanserin, a 5-HT2 receptor antagonist respectively. 5-HT, 8-OH-DPAT and DOI showed additive stimulatory effects with AVP but only at the highest concentration tested, whereas m-CPP potentiated AVP-induced ACTH release at concentrations of 1 nmol/l or more. This effect was antagonized by metergoline, a non-selective 5-HT receptor antagonist and mianserin, an antagonist which binds the 5-HT1C receptor with elevated affinity.(ABSTRACT TRUNCATED AT 250 WORDS)
Department of Internal Medicine, University of Catania, Italy.
A E
AE
Calogero
G
G
Bagdy
M L
ML
Moncada
R
R
D'Agata
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology; D000324:Adrenocorticotropic Hormone / Q000096:biosynthesis*; D000662:Amphetamines / Q000494:pharmacology; D000818:Animals; D001127:Arginine Vasopressin / Q000494:pharmacology; D002478:Cells, Cultured; D003346:Corticotropin-Releasing Hormone / Q000494:pharmacology; D008297:Male; D010879:Piperazines / Q000494:pharmacology; D010903:Pituitary Gland, Anterior / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011985:Receptors, Serotonin / Q000378:metabolism*; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*; D013268:Stimulation, Chemical
D000662:Amphetamines; D010879:Piperazines; D011985:Receptors, Serotonin; D017366:Serotonin Receptor Agonists; D001127:Arginine Vasopressin; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D000324:Adrenocorticotropic Hormone; D003346:Corticotropin-Releasing Hormone; C015952:4-iodo-2,5-dimethoxyphenylisopropylamine; C015068:1-(3-chlorophenyl)piperazine