Adenosine receptor-mediated inhibition of inositol 1,4,5 trisphosphate production in coronary artery

Previously, we indirectly showed that relaxation of porcine coronary artery by adenosine and its analogs are linked to modulation of phospholipase C and protein kinase C. In the present investigation, we assessed if the relaxant responses to the adenosine analogs CAD and NECA are associated with inhibition of inositol 1,4,5-trisphosphate (IP₃) formation. A protein binding assay system was used to measure the concentration of IP₃. IP, was generated by prostaglandin F_2α (20 μM) in coronary rings with and without endothelium. In both tissues, PGF_2α caused a rapid and transient elevation of IP₃ which reached a peak at 10 sec. Preincubation of tissues with either CAD or NECA caused a dose-related inhibition of the IP₃ produced by PGF_2α with a significant inhibition at higher doses. However, the inhibitory effect of NECA was relatively less in endothelium-intact rings. In addition, NECA by itself tended to increase the levels of basal IP₃ in the intact but not denuded tissues. CAD did not produce a significant effect on the basal IP₃ contents in both preparations. These results suggest that adenosine receptor activation in porcine coronary artery inhibits agonist-induced production of IP₃, and the magnitude of inhibition appears to depend on the type of adenosine analog used and on the presence and absence of endothelium. (Supported by HL-27339 and Minority Supplement to HI.-50049).