Effects of a platelet-released, naturally occurring nucleotide, adenosine 5'-tetraphosphate (ATPP) on vascular tone were analyzed in the isolated rat aorta. Under resting tension ATPP (1 ~ 100 μM) elicited concentration-dependent contractions in endothelium-intact aortic rings in contrast to the concentration-dependent relaxation with ATP. In endothelial-denuded aortic rings, ATPP induced contraction, as ATP did, but with a greater potency. α,β-methylene ATP (APCPP 50 μM), a P(2x)-purinoceptor antagonist, significantly inhibited ATPP- as well as ATP-induced contractions in the endothelium-denuded preparations suggesting that ATPP acts via P(2x)-purinoceptors. ATPP (10 ~ 100 μM) relaxed precontracted aortic rings with an intact endothelium in a concentration-dependent manner. This effect of ATPP was 3.7 fold less potent than that of ATP. However, after P(2x)-purinoceptor blockade, the effect became identical between the two nucleotides. Reactive blue 2, a selective antagonist of P(2x)-purinoceptors, significantly attenuated the ATPP-induced relaxation with no change in the ATP-induced relaxation. These results indicated that the rat aortic endothelium contains heterogeneous populations of P2-purinoceptors (possibly P(2y) and nucleotide receptors). Since ATPP shows dual effects depending upon the vascular tension, it may play a significant role in the physiological regulation of vascular tone.
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