Effect of selective serotonin (5-HT) agonists and 5-HT2 antagonist on prolactin secretion.
The present study was undertaken to determine the involvement of serotonergic 5-HT1 and 5-HT2 receptor subtypes in stimulation of the secretion of prolactin. Several 5-HT agonists were administered, in a dose-response fashion, to conscious rats and the effect on the levels of prolactin in plasma was measured. The 5-HT1A + 5-HT1B agonist RU 24969 (5-methoxy-3[1,2,3,6-tetrahydropyridin-4-yl]-1H-indole succinate) and the 5-HT1 + 5-HT2 agonist MK-212 (6-chloro-2-[1-piperazinyl]pirazine) increased levels of prolactin in plasma in a dose-dependent manner. In contrast, the selective 5-HT1A agonists 8-OH-DPAT (8-hydroxy-2-[di-n-propylamino]tetralin) and ipsapirone (2-[4-[4-(2-pyrimidinyl)-1-piperazinyl]butyl]-1,2-benzisothiazol-3 -(2H) one-1,1-dioxidehydrochloride) did not increase levels of prolactin in plasma at any dose. The 5-HT-releasing drug, fenfluramine, also increased the concentration of prolactin in plasma. Pretreatment with the selective 5-HT2 antagonist, LY53857 (6-methyl-1-[1-methylethyl]ergoline-8-carboxylic acid, 2-hydroxy-1-methyl propyl ester (Z)-2-butenedioate [1:1]), did not significantly diminish an increase in levels of prolactin in plasma, induced by injection of fenfluramine. The antagonist LY53857 inhibited, but did not block the MK-212- and RU 24969-induced increase in the levels of prolactin in plasma. By deduction, these data suggest that 5-HT1B receptors, or as yet undefined 5-HT receptor subtypes may be involved in the stimulation of the secretion of prolactin by endogenously released 5-HT, and that 5-HT2 receptors may play a minor role in the serotonergic regulation of the secretion of prolactin.
Van de Kar
L D
LD
Loyola University of Chicago, Stritch School of Medicine, Department of Pharmacology, Maywood, Illinois 60153.
Lorens
S A
SA
Urban
J H
JH
Bethea
C L
CL
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D000818:Animals; D004873:Ergolines / Q000494:pharmacology; D005277:Fenfluramine / Q000494:pharmacology; D007211:Indoles / Q000494:pharmacology; D008297:Male; D011388:Prolactin / Q000097:blood*; D011719:Pyrazines / Q000494:pharmacology; D011863:Radioimmunoassay; D051381:Rats; D011985:Receptors, Serotonin / Q000187:drug effects; D012701:Serotonin / Q000502:physiology*; D012702:Serotonin Antagonists / Q000494:pharmacology*; D013764:Tetrahydronaphthalenes / Q000494:pharmacology
D004873:Ergolines; D007211:Indoles; D011719:Pyrazines; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D013764:Tetrahydronaphthalenes; D005277:Fenfluramine; C025145:5-methoxy 3-(1,2,3,6-tetrahydro-4-pyridinyl)1H indole; D012701:Serotonin; C014896:6-chloro-2-(1-piperazinyl)pyrazine; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D011388:Prolactin; C032663:LY 53857