In vivo effects of serotonergic agents on alpha-melanocyte-stimulating hormone secretion.
We used an in vivo pharmacological approach to investigate the potential influence of serotonin (5-HT) on peptide release from the intermediate lobe (IL) of the rat pituitary. Plasma levels of alpha-melanocyte-stimulating hormone (alpha-MSH) as well as the ultrastructural appearance of IL cells were used as indicators of IL secretory activity. Plasma beta-endorphin levels were also measured to assess the effectiveness of 5-HT-acting drugs. Intraperitoneal administration of 5-hydroxy-L-tryptophan, the synthetic precursor of 5-HT, dramatically elevated the content of 5-HT in the neurointermediate lobe but did not alter plasma titers of alpha-MSH. Treatment with the 5-HT reuptake blocker fluoxetine elevated plasma levels of beta-endorphin but not alpha-MSH. Administration of the 5-HT1/5-HT2 agonist MK-212 produced an elevation in both plasma alpha-MSH and beta-endorphin levels. Quantitative morphometry of IL cells at the ultrastructural level revealed that MK-212 treatment selectively causes depletion of electron-lucent but not electron-dense secretory granules from the cytoplasm of IL cells. Pretreatment with the selective D2 dopamine agonist apomorphine blocked MK-212-induced release of alpha-MSH but not beta-endorphin. Our results show that manipulation of 5-HT synthesis/reuptake does not affect release of alpha-MSH, but that direct activation of 5-HT receptors with the nonselective agonist MK-212 stimulates alpha-MSH release. The ability of apomorphine to block MK-212-induced release of alpha-MSH suggests a direct antagonism between dopaminergic and serotonergic regulation of alpha-MSH release.
Carr
J A
JA
Department of Anatomy, School of Medicine, University of New Mexico, Albuquerque.
Saland
L C
LC
Samora
A
A
Benavidez
S
S
Krobert
K
K
D000818:Animals; D001058:Apomorphine / Q000494:pharmacology; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D003594:Cytoplasmic Granules / Q000378:metabolism / Q000648:ultrastructure; D008297:Male; D010902:Pituitary Gland / Q000378:metabolism / Q000648:ultrastructure; D011719:Pyrazines / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011954:Receptors, Dopamine / Q000502:physiology; D012701:Serotonin / Q000502:physiology*; D000521:alpha-MSH / Q000097:blood / Q000378:metabolism*; D001615:beta-Endorphin / Q000097:blood
D011719:Pyrazines; D011954:Receptors, Dopamine; D012701:Serotonin; D000521:alpha-MSH; D001615:beta-Endorphin; C014896:6-chloro-2-(1-piperazinyl)pyrazine; D001058:Apomorphine