P2 purinoceptor-mediated cyclic AMP accumulation in bovine vascular smooth muscle cells

Abstract Extracellular ATP has been shown to induce intracellular Ca 2+ mobilization and adenylate cyclase inhibition via P 2 purinoceptors in several species of cells. Now we found that in calf vascular smooth muscle cells the addition of ATP to the medium did not induce inhibition but stimulation of cyclic AMP accumulation, in addition to stimulation of inositol phosphate production. Adenosine and AMP also induced cyclic AMP accumulation but their efficacy was much less than that of ATP. The ATP action was not influenced by the presence of either adenosine deaminase or of an ATP regenerating system, whereas the AMP action was increased by the regenerating system. The results indicate that the cyclic AMP accumulation by ATP is due to ATP itself but neither to adenosine nor to AMP, both of which are produced from ATP. ATP receptor coupled to the cyclic AMP generation was shown to be different from that coupled to phospholipase C based on the difference in the potency order of the receptor agonists and in the sensitivity of P 2 receptor agonists to 8-cyclopentyl-1,3-dipropylxanthine (CPX)- andd suramin-induced antagonis. We conclude that in the aortic smooth muscle cells a novel P 2 -type receptor directly coupled to adenylate cyclase activation exists in addition to the previously known P 2 receptor linked to phospholipase C activation.