Neuroendocrine evidence for denervation supersensitivity of serotonin receptors: effects of the 5-HT agonist RU 24969 on corticotropin, corticosterone, prolactin and renin secretion.
Serotonergic stimulation can increase the secretion of several hormones through the involvement of different serotonin (5-HT) receptor subtypes. RU 24969, a 5-HT agonist with highest affinity at 5-HT1A and 5-HT1B receptors, increased plasma renin activity (PRA) and plasma renin concentration (PRC) as well as plasma corticosterone and prolactin concentrations in a dose-dependent manner. Inasmuch as 5-HT2 receptors mediate the serotonergic stimulation of renin secretion, we examined the ability of two selective 5-HT2 antagonists, ritanserin and LY53857, to inhibit the neuroendocrine effects of RU 24969. To determine whether the 5-HT receptors which are involved in the stimulation of these hormones are pre- or postsynaptic, RU 24969 was also injected to rats whose brain serotonergic neurons were chemically destroyed by i.c.v. injection of 5,7-dihydroxytryptamine. Both ritanserin and LY53857 blocked the effect of RU 24969 on PRA and PRC, but did not inhibit the RU 24969-induced elevation in plasma corticosterone concentrations. Ritanserin did not inhibit the effect of RU 24969 on prolactin levels, but LY53857 produced a partial inhibition of the RU 24969-induced elevation of prolactin concentrations. In rats with chemical lesions of serotonergic neurons the dose-response curves of RU 24969 for PRA and PRC as well as corticotropin, corticosterone and prolactin shifted to the left, suggesting functional up-regulation of postsynaptic 5-HT receptors.(ABSTRACT TRUNCATED AT 250 WORDS)
Van de Kar
L D
LD
Department of Pharmacology, Stritch School of Medicine, Loyola University of Chicago, Maywood, Illinois.
Carnes
M
M
Maslowski
R J
RJ
Bonadonna
A M
AM
Rittenhouse
P A
PA
Kunimoto
K
K
Piechowski
R A
RA
Bethea
C L
CL
D000324:Adrenocorticotropic Hormone / Q000378:metabolism*; D000818:Animals; D003345:Corticosterone / Q000378:metabolism*; D003714:Denervation; D004873:Ergolines / Q000494:pharmacology; D007211:Indoles / Q000494:pharmacology*; D008297:Male; D011388:Prolactin / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D011985:Receptors, Serotonin / Q000032:analysis / Q000502:physiology*; D012083:Renin / Q000378:metabolism*
D004873:Ergolines; D007211:Indoles; D011985:Receptors, Serotonin; C025145:5-methoxy 3-(1,2,3,6-tetrahydro-4-pyridinyl)1H indole; D000324:Adrenocorticotropic Hormone; D011388:Prolactin; D012083:Renin; C032663:LY 53857; D003345:Corticosterone