Relative agonist potencies of C2-substituted analogues of adenosine: evidence for adenosine A2B receptors in the guinea pig aorta

Eur J Pharmacol. 1992 Jun 5;216(2):235-42. doi: 10.1016/0014-2999(92)90365-b.


Nine C2-substituted adenosine analogues that are potent and selective for the A2-adenosine receptor were tested for their ability to induce relaxations of the guinea pig aorta. Compounds tested were 2-phenylethoxyadenosine (PEA), 2-phenylethoxy-5'-N-ethylcarboxamidoadenosine (PENECA), 2-cyclohexylethoxyadenosine (CEA), 2-fluorophenylethoxyadenosine (FPEA), 2-methoxyphenylethoxyadenosine (MPEA), 2-naphthylethoxyadenosine (NEA), 2-phenylaminoadenosine (CV-1808), 2-phenylethylaminoadenosine (PEAA) and 2-carboxyethylphenethylamino-5'-N-ethylcarboxamidoadenosine (CGS21680). The responses to these agents were compared to those of three standard adenosine receptor agonists, 5'-N-ethylcarboxamidoadenosine (NECA), N6-cyclohexyladenosine (CHA) and R-N6-phenylisopropyladenosine (R-PIA). The C2-ethoxyadenosine analogues were 30- to 140-fold less potent than NECA and the C2-amino-substituted analogues were 250 to 1000-fold less potent than NECA at inducing relaxations of the guinea pig aorta. All of the analogues were also less potent than the A1-selective agonist R-PIA. However, only responses to NECA were competitively antagonized by the non-selective adenosine receptor antagonist 8-phenyltheophylline (8-PT), pKB = 6.83 +/- 0.05. The results suggest that the C2-substituted analogues produce relaxations of the guinea pig aorta through a combination of actions at A2-adenosine receptors and at xanthine resistant sites. The lack of potency of these analogues at activating the xanthine sensitive A2-receptors in the guinea pig aorta suggests that these adenosine receptors may be of the A2b-subtype.

MeSH terms

  • Adenosine / analogs & derivatives*
  • Adenosine / pharmacology*
  • Adenosine-5'-(N-ethylcarboxamide)
  • Animals
  • Aorta, Thoracic / drug effects*
  • Dose-Response Relationship, Drug
  • Endothelium, Vascular / drug effects
  • Endothelium, Vascular / physiology
  • Guinea Pigs
  • Male
  • Muscle, Smooth, Vascular / drug effects*
  • Muscle, Smooth, Vascular / physiology
  • Phenethylamines / pharmacology
  • Receptors, Purinergic / classification
  • Receptors, Purinergic / drug effects*
  • Theophylline / analogs & derivatives
  • Theophylline / pharmacology
  • Vasodilator Agents / pharmacology


  • Phenethylamines
  • Receptors, Purinergic
  • Vasodilator Agents
  • 2-(4-(2-carboxyethyl)phenethylamino)-5'-N-ethylcarboxamidoadenosine
  • Adenosine-5'-(N-ethylcarboxamide)
  • Theophylline
  • 8-phenyltheophylline
  • Adenosine