Pharmacological evidence that 5-HT(1B/1D) receptors mediate hypotension in anesthetized rats

Eur J Pharmacol. 2007 Dec 8;576(1-3):132-5. doi: 10.1016/j.ejphar.2007.08.005. Epub 2007 Aug 14.

Abstract

5-Carboxamidotryptamine (5-CT; 0.003-310 microg/kg, i.v.) produced dose-dependent hypotensive responses which were blocked in a complex manner by the 5-HT(7) receptor antagonist, (R)-1-[(3-hydroxyphenyl)sulfonyl]-2-[2-(4-methyl-1-piperidinyl) ethyl] pyrrolidine (SB-269970; 1 mg/kg, i.v.), in anesthetized vagosympathectomized rats. Interestingly, the 5-HT(1B/1D) receptor antagonist, N-[4-methoxy-3-(4-methyl-1-piperazinyl) phenyl]-2'-methyl-4'-(5-methyl-1,2,4-oxadiazol-3-yl) [1,1-biphenyl]-4-carboxamide hydrochloride monohydrate GR-127935 (1 mg/kg, i.v.), also inhibited 5-CT-induced hypotension but the effect was clearly noncompetitive. Finally, the combination of GR-127935+SB-269970 (1 mg/kg, i.v., each) produced a further decreased of 5-CT-induced responses as compared to the effect of individual treatments. These data suggest that, in addition to 5-HT(7) receptors, 5-HT(1B/1D) receptors may also mediate hypotension in rats.

MeSH terms

  • Anesthesia
  • Animals
  • Blood Pressure / drug effects
  • Hypotension / physiopathology*
  • Male
  • Oxadiazoles / pharmacology
  • Phenols / pharmacology
  • Piperazines / pharmacology
  • Rats
  • Rats, Wistar
  • Receptor, Serotonin, 5-HT1B / physiology*
  • Receptor, Serotonin, 5-HT1D / physiology*
  • Receptors, Serotonin / physiology*
  • Serotonin / analogs & derivatives
  • Serotonin / pharmacology
  • Serotonin 5-HT1 Receptor Agonists
  • Serotonin 5-HT1 Receptor Antagonists
  • Serotonin Antagonists / pharmacology
  • Serotonin Receptor Agonists / pharmacology
  • Sulfonamides / pharmacology

Substances

  • 5-HT(7) receptor, rat
  • Oxadiazoles
  • Phenols
  • Piperazines
  • Receptor, Serotonin, 5-HT1B
  • Receptor, Serotonin, 5-HT1D
  • Receptors, Serotonin
  • SB 269970
  • Serotonin 5-HT1 Receptor Agonists
  • Serotonin 5-HT1 Receptor Antagonists
  • Serotonin Antagonists
  • Serotonin Receptor Agonists
  • Sulfonamides
  • GR 127935
  • Serotonin
  • 5-carboxamidotryptamine