Neuroendocrine evidence for denervation supersensitivity of serotonin receptors: Effects of the 5-HT agonist RU 24969 on corticotropin, corticosterone, prolactin and renin secretion

L. D. Van De Kar, M. Carnes, R. J. Maslowski, A. M. Bonadonna, P. A. Rittenhouse, K. Kunimoto, R. A. Piechowski, C. L. Bethea

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    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.

    Original languageEnglish (US)
    Pages (from-to)428-434
    Number of pages7
    JournalJournal of Pharmacology and Experimental Therapeutics
    Issue number2
    StatePublished - Jan 1 1989


    ASJC Scopus subject areas

    • Molecular Medicine
    • Pharmacology

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