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 language||English (US)|
|Number of pages||7|
|Journal||Journal of Pharmacology and Experimental Therapeutics|
|State||Published - 1989|
ASJC Scopus subject areas
- Molecular Medicine