Cardiovascular and antilipolytic effects of the adenosine agonist GR79236

Pharmacology. 1995 Oct;51(4):224-36. doi: 10.1159/000139364.

Abstract

Adenosine is known to produce cardiovascular effects such as bradycardia and hypotension via activation of myocardial (A1) and vascular (A2) receptors and antilipolytic effects through activation of adipocyte (A1) receptors. We established the cardiovascular and antilipolytic profile of the adenosine A1 agonist GR79236 (N6-[(1S,trans)-2-hydroxycyclopentyl]-adenosine) and compared it with CPA (N6-cyclopentyl-adenosine). GR79236 was approximately 3-fold less potent than CPA in inhibiting in vitro lipolysis. In conscious rats, both agents were shown to have antilipolytic and glucose-lowering properties. In rats instrumented with telemetry transmitters, orally administered CPA was one log unit more potent than GR79236 as a hypotensive and bradycardiac agent. In summary, GR79236 is an A1-selective adenosine agonist which reduces heart rate and mean arterial pressure and produces decreased plasma lipids and glucose levels.

Publication types

  • Comparative Study

MeSH terms

  • Adenosine / administration & dosage
  • Adenosine / analogs & derivatives*
  • Adenosine / pharmacology
  • Adipocytes / drug effects*
  • Administration, Oral
  • Analysis of Variance
  • Animals
  • Blood Glucose / metabolism
  • Blood Pressure / drug effects
  • Cross-Over Studies
  • Heart Rate / drug effects
  • Hypolipidemic Agents / administration & dosage
  • Hypolipidemic Agents / pharmacology*
  • In Vitro Techniques
  • Infusions, Intravenous
  • Lipids / blood
  • Lipolysis / drug effects
  • Male
  • Motor Activity / drug effects
  • Purinergic P1 Receptor Agonists*
  • Radioligand Assay
  • Rats
  • Rats, Sprague-Dawley
  • Telemetry

Substances

  • Blood Glucose
  • Hypolipidemic Agents
  • Lipids
  • Purinergic P1 Receptor Agonists
  • N(6)-cyclopentyladenosine
  • Adenosine
  • N-((1S,trans)-2-hydroxycyclopentyl)adenosine