Effects of adenosine tetraphosphate (ATPP) on vascular tone in the isolated rat aorta

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 approximately 100 microM) elicited concentration-dependent contractions in endothelium-intact aortic rings in contrast to the concentration-dependent relaxation with ATP. In endothelium-denuded aortic rings, ATPP induced contraction, as ATP did, but with a greater potency. alpha, beta-methylene ATP (APCPP 50 microM), a P2x-purinoceptor antagonist, significantly inhibited ATPP- as well as ATP-induced contractions in the endothelium-denuded preparations suggesting that ATPP acts via P2x-purinoceptors. ATPP (10 approximately 100 microM) 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 P2x-purinoceptor blockade, the effect became identical between the two nucleotides. Reactive blue 2, a selective antagonist of P2x-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 P2y 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.

Progress in the studies of P_2 purinoceptors / 中国药理学通报

P 2 purinoceptors were first subdivided into P 2X and P 2Y subtypes, and later this classification was broadened to include P 2T , P 2Z and P 2D subtypes. In the 1990s, a new kind of receptors was found, which respond to UTP, ATP and ATP?S, but not to 2 MeSATP or ?,? MeATP, this finding led to the definition of the so called “P 2U ” or “nucleotide” receptor. Most recent evidence demonstrated the existence of a pyrimidine receptor responding to UTP but not to ATP. For this case, IUPHAR (International Union of Pharmacology) committee recommended that P 2 purinoceptors be subdivided into P2X and P2Y subtypes, any subtypes of intrinsic ion channel be termed P2Xn, and any subtypes of G protein coupled receptor be termed P2Yn purinoceptors. With the development and application of the molecular biologic technique and the cloning and expression of the receptors, the classification was strongly confirmed.