TY - JOUR
T1 - Neuroendocrine evidence for denervation supersensitivity of serotonin receptors
T2 - Effects of the 5-HT agonist RU 24969 on corticotropin, corticosterone, prolactin and renin secretion
AU - Van De Kar, L. D.
AU - Carnes, M.
AU - Maslowski, R. J.
AU - Bonadonna, A. M.
AU - Rittenhouse, P. A.
AU - Kunimoto, K.
AU - Piechowski, R. A.
AU - Bethea, C. L.
N1 - Copyright:
Copyright 2004 Elsevier B.V., All rights reserved.
PY - 1989
Y1 - 1989
N2 - 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-HT(1A) and 5-HT(1B) 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. The present results suggest that: 1) RU 24969 also activates 5-HT2 receptors; 2) 5-HT2 receptors are not appreciably involved in prolactin release; 3) the 5-HT receptors responsible for the stimulation of renin, corticotropin, corticosterone and prolactin secretion are located postsynaptically; and 4) denervation increases the functional neuroendocrine response to 5-HT agonists which can activate 5-HT(1A), 5-HT(1B) and 5-HT2 receptors.
AB - 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-HT(1A) and 5-HT(1B) 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. The present results suggest that: 1) RU 24969 also activates 5-HT2 receptors; 2) 5-HT2 receptors are not appreciably involved in prolactin release; 3) the 5-HT receptors responsible for the stimulation of renin, corticotropin, corticosterone and prolactin secretion are located postsynaptically; and 4) denervation increases the functional neuroendocrine response to 5-HT agonists which can activate 5-HT(1A), 5-HT(1B) and 5-HT2 receptors.
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M3 - Article
C2 - 2553918
AN - SCOPUS:0024351523
SN - 0022-3565
VL - 251
SP - 428
EP - 434
JO - Journal of Pharmacology and Experimental Therapeutics
JF - Journal of Pharmacology and Experimental Therapeutics
IS - 2
ER -