Effects of adenosine analogs on inositol 1,4,5-trisphosphate production in porcine coronary artery.
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 F2 alpha (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.
Abebe
Worku
W
Department of Oral Biology and Maxillofacial Pathology, School of Dentistry, CB 3710, Medical College of Georgia, Augusta, GA 30912-2118, USA. wabebe@mail.mcg.edu
Mustafa
S Jamal
SJ
D000241:Adenosine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D000818:Animals; D003331:Coronary Vessels / Q000187:drug effects* / Q000378:metabolism; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism; D066298:In Vitro Techniques; D015544:Inositol 1,4,5-Trisphosphate / Q000096:biosynthesis*; D008297:Male; D058906:Purinergic P1 Receptor Agonists; D018047:Receptors, Purinergic P1 / Q000378:metabolism; D013552:Swine
D058906:Purinergic P1 Receptor Agonists; D018047:Receptors, Purinergic P1; D015544:Inositol 1,4,5-Trisphosphate; D000241:Adenosine