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Differential Effects of Serotonin (5-HT1A and 5-HT2) Agonists and Antagonists on Renin and Corticosterone SecretionLorens S.A. · Van de Kar L.D.
Department of Pharmacology, Stritch School of Medicine, Loyola University of Chicago, Maywood, Ill., USA
The present study was designed to investigate the effect of distinct serotonin (5-HT1A and 5-HT2) agonists and antagonists on renin and corticosterone secretion. Low doses of the selective 5-HT1A agonists 8-hydroxy-2-(di-N-propylamino)tetralin (8-OH-DPAT) (5.0–500.0 µg/kg, i.p.) and ipsapirone (TVX Q 7821; 0.5–2.5 mg/kg, i.p.), and of the 5-hy-droxytryptamine (5-HT) agonist MK-212 (2.0 mg/kg, i.p.), did not elevate plasma renin activity (PRA) and concentration (PRC) 30 min postinjection. Administration of a higher dose of MK-212 (10.0 mg/kg, i.p.) and of higher doses of ipsapirone (5.0–10.0 mg/kg, i.p.), as well as the 5-HT releaser, fenfluramine (5.0 mg/kg, i.p.), resulted in large increases in PRA and PRC. The effects of MK-212 and fenfluramine on PRA and PRC were blocked by pretreatment with the selective 5-HT2 antagonist, LY53857, in a dose-dependent (0.3–1.0 mg/kg, i.p.) manner. LY53857 (1.0 mg/kg, i.p.) by itself did not affect PRA or PRC. LY53857, furthermore, unmasked a renin-suppressive effect of MK-212, since injection of MK-212 (10.0 mg/kg, i.p.) following LY53857 administration led to a reduction in PRA and PRC. MK-212 (2.0 and 10.0 mg/kg), the high doses of 8-OH-DPAT (500.0 µg/kg), ipsapirone (1.0–10.0 mg/kg), and fenfluramine (5.0 mg/kg) all produced an increase in plasma corticosterone levels. The effects of MK-212 and fenfluramine on corticosterone were not inhibited by pretreatment with LY53857. These data suggest that 5-HTIA receptors do not play a role in the regulation of renin secretion, whereas stimulation of 5-HT2 receptors enhances renin release. The data also suggest that MK-212- and fenfluramine-induced corticosterone secretion is not mediated by 5-HT2 receptors.
© 1987 S. Karger AG, Basel