Investigation of the role of 5-HT3 receptors in the secretion of prolactin, ACTH and renin.
The potential roles of central and peripheral 5-HT3 receptors in the secretion of prolactin, adrenocorticotropic hormone (ACTH), corticosterone and renin was investigated. Male rats received the 5-HT3 antagonist ondansetron (0, 0.1 or 1 mg/kg i.p.), 30 min prior to injections of the serotonin (5-HT) releaser, p-chloroamphetamine (PCA; 0, 3 or 8 mg/kg i.p.). Blood samples were collected 60 min after PCA for radioimmunoassays of plasma prolactin, ACTH, corticosterone and renin concentrations. PCA significantly elevated secretion of each of these hormones. Pretreatment with the 5-HT3 antagonist, ondansetron, significantly attenuated the PCA-induced elevation of prolactin secretion, suggesting that 5-HT3 receptors contribute to the serotonergic stimulation of prolactin secretion. Ondansetron did not modify effects of PCA on ACTH, corticosterone or renin secretion. To determine whether the 5-HT3 receptor role in prolactin secretion is mediated in the brain, the endocrine effects of intracerebroventricular (i.c.v.) injections of 5-HT (30 micrograms/kg) or the 5-HT3 agonist, 2-methylserotonin (1, 20 or 200 micrograms/kg) were evaluated. Both 5-HT and 2-methylserotonin significantly elevated plasma prolactin levels 15 min postinjection. However, ondansetron (1 mg/kg i.p.) did not antagonize these actions. Both 5-HT and 2-methylserotonin also increased plasma ACTH and corticosterone concentrations. Finally, 5-HT suppressed, while 2-methylserotonin stimulated renin secretion. None of the hormonal effects of i.c.v. injected 5-HT or 2-methylserotonin were altered by ondansetron. Thus, the results suggest that peripheral, but not central 5-HT3 receptors are involved in the stimulation of prolactin secretion. Furthermore, 5-HT3 receptors do not mediate the serotonergic stimulation of ACTH, corticosterone, or renin secretion.
Levy
A D
AD
Department of Pharmacology, Loyola University Chicago, Maywood, Ill 60153.
Li
Q
Q
Rittenhouse
P A
PA
Van de Kar
L D
LD
D000324:Adrenocorticotropic Hormone / Q000378:metabolism*; D000818:Animals; D002552:Cerebral Ventricles; D007263:Infusions, Parenteral; D008297:Male; D017294:Ondansetron / Q000494:pharmacology; D011388:Prolactin / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011985:Receptors, Serotonin / Q000502:physiology*; D012083:Renin / Q000378:metabolism*; D012701:Serotonin / Q000008:administration & dosage / Q000031:analogs & derivatives; D010133:p-Chloroamphetamine
D011985:Receptors, Serotonin; D012701:Serotonin; D017294:Ondansetron; D010133:p-Chloroamphetamine; C045918:2-methyl-5-HT; D000324:Adrenocorticotropic Hormone; D011388:Prolactin; D012083:Renin