NEURO-ENDOCRINE EVIDENCE FOR DENERVATION SUPERSENSITIVITY OF SEROTONIN RECEPTORS - EFFECTS OF THE 5-HT AGONIST RU-24969 ON CORTICOTROPIN, CORTICOSTERONE, PROLACTIN AND RENIN SECRETION

Abstract

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)