The novel pyridoxal-5 '-phosphate derivative PPNDS potently antagonizes activation of P2X(1) receptors

Pyridoxal-5'-phosphate-6-(2'-naphthylazo-6'-nitro-4',8'-disulfonate) (PPNDS ) potently antagonized P2X(1) receptor-mediated responses in rat vas defere ns (pK(B) = 7.43) and Xenopus laevis oocytes (pIC(50) = 7.84). It showed lo wer (up to 20,000-fold) inhibitory potency on ecto-nucleotidase in Xenopus oocytes and on P2Y(1) receptors in guinea-pig ileum (pA(2) = 6.13). PPNDS d id not interact with alpha(1A)-adrenoceptors, adenosine A(1) and A(2B), his tamine H-1 and muscarinic M-3 receptors. Thus, PPNDS is a novel, specific P 2 receptor antagonist and represents the pyridoxal-5'-phosphate derivative with the highest potency at P2X(1) receptors. (C) 2000 Elsevier Science B.V . All rights reserved.