Differential effects of serotonin (5-HT1A and 5-HT2) agonists and antagonists on renin and corticosterone secretion.
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 micrograms/kg, i.p.) and ipsapirone (TVX Q 7821; 0.5-2.5 mg/kg, i.p.), and of the 5-hydroxytryptamine (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 micrograms/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-HT1A receptors do not play a role in the regulation of renin secretion, whereas stimulation of 5-HT2 receptors enhances renin release.(ABSTRACT TRUNCATED AT 250 WORDS)
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D000818:Animals; D003345:Corticosterone / Q000378:metabolism*; D004873:Ergolines / Q000494:pharmacology; D005277:Fenfluramine / Q000494:pharmacology; D008297:Male; D011719:Pyrazines / Q000494:pharmacology; D011743:Pyrimidines / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011985:Receptors, Serotonin / Q000145:classification / Q000187:drug effects; D012083:Renin / Q000378:metabolism*; D012701:Serotonin / Q000502:physiology*; D012702:Serotonin Antagonists / Q000494:pharmacology*; D013764:Tetrahydronaphthalenes / Q000494:pharmacology
D004873:Ergolines; D011719:Pyrazines; D011743:Pyrimidines; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D013764:Tetrahydronaphthalenes; D005277:Fenfluramine; D012701:Serotonin; C014896:6-chloro-2-(1-piperazinyl)pyrazine; C043077:ipsapirone; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D012083:Renin; C032663:LY 53857; D003345:Corticosterone