Effects of adenosine analogs on inositol 1,4,5-trisphosphate production in porcine coronary artery

Worku Abebe, S. Jamal Mustafa

Research output: Contribution to journalArticle

6 Scopus citations

Abstract

Using various pharmacological methods, we previously demonstrated that the smooth muscle and endothelium of porcine coronary artery contain vasorelaxant adenosine A2 receptors, which are predominantly the A2A subtype. The present study was intended to investigate the effect of adenosine receptor stimulation on agonist-induced inositol 1,4,5-trisphosphate (IP3) generation in porcine coronary artery using the nonselective adenosine analogs, 2-chloroadenosine (CAD) and 5′-(N-ethylcarboxamido)adenosine (NECA), and the A2A selective analog 2-p-(2-carboxyethyl)-phenethylamino-5′-N-ethylcarboxamidoadenosine (CGS). In both endothelium-intact and denuded coronary artery rings, CAD, NECA and CGS elicited a dose-dependent inhibition of prostaglandin F (PG)-induced IP3 production. However, the inhibitory effect of NECA was relatively less in endothelium-denuded preparations. The nonselective xanthine adenosine receptor antagonist, 8-sulfophenyltheophylline (8-SPT), significantly attenuated the IP3-inhibitory effect of CAD and, to a lesser extent, that of NECA. Further, the A2A selective nonxanthine antagonist, 5-amino-7-(2-phenylethyl)-2-(-furyl)-pyrazolo[4,3]-1,2,4-triazolo[1,5-c] pyrimidine (SCH), markedly decreased the effects of all CAD, NECA and CGS on PG-induced IP3 generation. These results provide evidence that activation of adenosine A2 receptors by CAD, NECA and CGS in porcine coronary artery causes inhibition of agonist-induced IP3 production, and these receptors involve at least the A2A subtype.

Original languageEnglish (US)
Pages (from-to)89-95
Number of pages7
JournalVascular Pharmacology
Volume39
Issue number1-2
DOIs
Publication statusPublished - Jul 1 2002

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Keywords

  • Adenosine A receptors
  • Adenosine analogs
  • Inositol 1,4,5-trisphosphate
  • Porcine coronary artery

ASJC Scopus subject areas

  • Physiology
  • Molecular Medicine
  • Pharmacology

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