title: Antagonists and the purinergic nerve hypothesis: 2, 2'-pyridylisatogen tosylate (PIT), an allosteric modulator of P2Y receptors. A retrospective on a quarter century of progress.
abstract: 2,2'-Pyridylisatogen tosylate (PIT) is a selective antagonist of P2Y responses in smooth muscle and does not antagonise the effects of adenosine. Responses to purinergic nerve stimulation are resistant to PIT. PIT is an allosteric modulator of responses to ATP in recombinant P2Y(1) receptors expressed in Xenopus oocytes with potentiation of ATP at low concentrations (0.1-10 microM) and antagonism at higher ones (>10 microM). A radioligand binding profile showed that PIT did not interact with any other receptors, with the exception of low affinity for the adenosine A(1) receptor (pK(i), 5.3). The compound recognises purine sites and then may cause irreversible binding to sulfhydryl groups following prolonged incubation or high concentrations. PIT is a potent spin trapper.
authors.affiliation: Institut de Recherches Internationales Servier, 192 Avenue Charles de Gaulle, 92200, Neuilly sur Seine, France.
authors.forename: M
authors.initials: M
authors.lastname: Spedding
authors.forename: K
authors.initials: K
authors.lastname: Menton
authors.forename: A
authors.initials: A
authors.lastname: Markham
authors.forename: D F
authors.initials: DF
authors.lastname: Weetman
mesh_terms: D000255:Adenosine Triphosphate / Q000037:antagonists & inhibitors; D000818:Animals; D006801:Humans; D007510:Isatin / Q000031:analogs & derivatives* / Q000494:pharmacology; D009130:Muscle, Smooth / Q000187:drug effects; D058919:Purinergic P2 Receptor Antagonists; D018048:Receptors, Purinergic P2 / Q000502:physiology*
chemical_list: D058919:Purinergic P2 Receptor Antagonists; D018048:Receptors, Purinergic P2; C009128:2,2'-pyridylisatogen tosylate; D007510:Isatin; D000255:Adenosine Triphosphate