Effects of adenosine 3′-phosphate 5′-phosphosulfate on P2 receptors in platelets and smooth muscle preparations

Adenosine 3'-phosphate 5'-phosphosulfate (A3P5PS) has been proposed to be a selective antagonist at P2Y(1) receptors and this receptor subtype has been suggested to be present on human platelets and to be responsible for ADP-induced aggregation. The effects of A3P5PS, therefore, were tested on the responses of human platelets to ADP and also on the relaxation of the rat duodenum, which is also thought to be mediated by means of the P2Y(1) receptor, as well as on the contraction of the vas deferens and urinary bladder, which is thought to be mediated by means of P2X(1) receptors, because the effects of A3P5PS on P2X(1) receptors have not been reported. A3P5PS selectively antagonised in an apparently competitive manner ADP-induced platelet aggregation, as well as the ability of ADP to cause shape change and increases in [Ca2+](i) in platelets, but had no effect on the inhibition of stimulated adenylate cyclase by ADP, confirming suggestions that this response is mediated by means of a different receptor subtype. A3P5PS did not act as an antagonist in any of the smooth muscle preparations tested, but instead acted as an agonist in the rat duodenum, showing that there are limitations to its use in isolated tissue studies. In addition, A3P5PS was rapidly degraded by enzymes present on the surface of the rat vas deferens, and although its breakdown was slower than that of ATP itself, it may also be a complicating factor in the use of this and similar compounds. (C) 1998 Wiley-Liss, Inc.