Effects of serotonergic agonists and antagonists on corticotropin-releasing hormone secretion by explanted rat hypothalami

• Published in: Peptides (New York, N.Y. : 1980) Vol. 10; no. 1; pp. 189 - 200
• Main Authors: Calogero, Aldo E., Bernardini, Renato, Margioris, Andrew N., Bagdy, Gyorgy, Gallucci, William T., Munson, Peter J., Tamarkin, Lawrence, Tomai, Thomas P., Brady, Linda, Gold, Philip W., Chrousos, George P.
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 1989; Elsevier Science
• Subjects: 8-OH-DPAT; Animals; Biological and medical sciences; Corticotropin-releasing hormone; Corticotropin-Releasing Hormone - metabolism; DOI; Fundamental and applied biological sciences. Psychology; Hormones and neuropeptides. Regulation; Hypothalamus - cytology; Hypothalamus - drug effects; Hypothalamus - metabolism; Hypothalamus - ultrastructure; Hypothalamus. Hypophysis. Epiphysis. Urophysis; In Vitro Techniques; Ketanserin; m-CPP; Male; Metergoline; Microscopy, Electron; Radioimmunoassay; Rat hypothalamus; Rats; Rats, Inbred Strains; Ritanserin; Serotonin (5HT 1A and 5HT 2) receptors; Serotonin - pharmacology; Serotonin Antagonists - pharmacology; Vertebrates: endocrinology; Serotonin (5HT 1A and 5HT 2) receptors; Metergoline; m-CPP; Rat hypothalamus; Corticotropin-releasing hormone; 8-OH-DPAT; Ritanserin; DOI; Ketanserin; Rat; Serotonin; Secretion; Rodentia; ACTH-RH; Peptide hormone; Central nervous system; Explant; Hypothalamus; Hypothalamic hormone; Vertebrata; Mammalia; Neurotransmitter; Diencephalon; Hormone releasing factor
• ISSN: 0196-9781; 1873-5169
• DOI: 10.1016/0196-9781(89)90096-X

Experimental evidence suggests that serotonin (5HT) is excitatory to the hypothalamic-pituitary-adrenal axis and that this effect involves activation of both hypothalamic corticotropin-releasing hormone (CRH) and pituitary ACTH secretion. The present study was undertaken to examine the mechanism by which 5HT stimulates the central component of the HPA axis. To accomplish this we employed an in vitro rat hypothalamic organ culture system in which CRH secretion from single explanted hypothalami was measured by specific radioimmunoassay (IR-rCRH). All experiments were performed after an overnight (15–18 hr) preincubation. Serotonin stimulated IR-rCRH secretion in a dose-dependent fashion. The response was bell-shaped and the peak effect was observed at the concentration of 10 −9 M. The stimulatory effect of 10 −9 M 5HT was antagonized by the 5HT 1 and 5HT 2 receptor antagonist metergoline and by the selective 5HT 2 receptor antagonists ketanserin and ritanserin. The muscarinic antagonist atropine, the nicotinic antagonist hexamethonium and the α-adrenergic receptor antagonist phentolamine, on the other hand, did not inhibit 5HT-induced IR-rCRH secretion. The specific 5HT 2 receptor agonist 1-(2,5-dimethoxy-4-iodo-phenyl)-2-aminopropane (DOI) stimulated IR-rCRH secretion in a dose-dependent fashion. The response was bell-shaped with peak of effect reached at the concentration of 10 −9 M. We also tested the ability of the 5HT agonist meta-chlorophenylpiperazine (m-CPP) and of the selective 5HT 1A receptor agonist 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT) to cause CRH secretion. Although both m-CPP and 8-OH-DPAT stimulated IR-rCRH secretion in a dose-dependent fashion, several differences were observed when their effect was compared to that of 5HT. These included a different shape of the dose-response curve, a lower maximal stimulatory effect and a different maximal stimulatory concentration. These findings suggest that serotonin stimulates CRH secretion by explanted rat hypothalami and that this effect appears to be mediated mainly through a 5HT 2 receptor mechanism.