P2 purinoceptor-mediated cyclic AMP accumulation in bovine vascular smooth muscle cells.
Extracellular ATP has been shown to induce intracellular Ca2+ mobilization and adenylate cyclase inhibition via P2 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 P2 receptor agonists to 8-cyclopentyl-1,3-dipropylxanthine (CPX)- and suramin-induced antagonism. We conclude that in the aortic smooth muscle cells a novel P2-type receptor directly coupled to adenylate cyclase activation exists in addition to the previously known P2 receptor linked to phospholipase C activation.
Tada
S
S
Department of Physiological Chemistry, Faculty of Pharmaceutical Science, University of Tokyo, Japan.
Okajima
F
F
Mitsui
Y
Y
Kondo
Y
Y
Ui
M
M
D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D002417:Cattle; D000242:Cyclic AMP / Q000378:metabolism*; D066298:In Vitro Techniques; D007295:Inositol Phosphates / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000378:metabolism*; D011983:Receptors, Purinergic / Q000502:physiology*; D013498:Suramin / Q000494:pharmacology; D014316:Tritium
D007295:Inositol Phosphates; D011983:Receptors, Purinergic; D014316:Tritium; D013498:Suramin; D000255:Adenosine Triphosphate; D000242:Cyclic AMP