Antagonists and the purinergic nerve hypothesis: 2,2 '-pyridylisatogen tosylate (PIT), an allosteric modulator of P2Y receptors. A retrospective on aquarter century of progress

2,2'-Pyridylisatogen tosylate (PIT) is a selective antagonist of P2Y respon ses in smooth muscle and does not antagonise the effects of adenosine. Resp onses to purinergic nerve stimulation are resistant to PIT. PIT is an allos teric modulator of responses to ATP in recombinant P2Y(1) receptors express ed in Xenopus oocytes with potentiation of ATP at low concentrations (0.1-1 0 mu M) and antagonism at higher ones (>10 mu M). A radioligand binding pro file showed that PIT did not interact with any other receptors, with the ex ception of low affinity for the adenosine A(1) receptor (pK(i), 5.3). The c ompound recognises purine sites and then may cause irreversible binding to sulfhydryl groups following prolonged incubation or high concentrations. PI T is a potent spin trapper. (C) 2000 Elsevier Science B.V. All rights reser ved.