The novel pyridoxal-5'-phosphate derivative PPNDS potently antagonizes activation of P2X(1) receptors.
Pyridoxal-5'-phosphate-6-(2'-naphthylazo-6'-nitro-4',8'-disulfonat e) (PPNDS) potently antagonized P2X(1) receptor-mediated responses in rat vas deferens (pK(B)=7.43) and Xenopus laevis oocytes (pIC(50)=7. 84). It showed lower (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 did not interact with alpha(1A)-adrenoceptors, adenosine A(1) and A(2B), histamine H(1) and muscarinic M(3) receptors. Thus, PPNDS is a novel, specific P2 receptor antagonist and represents the pyridoxal-5'-phosphate derivative with the highest potency at P2X(1) receptors.
Lambrecht
G
G
Department of Pharmacology, Biocentre Niederursel, University of Frankfurt, Geb. N260, Marie-Curie-Str. 9, D-60439, Frankfurt, Germany. lambrecht@em.uni-frankfurt.de
Rettinger
J
J
Bäumert
H G
HG
Czeche
S
S
Damer
S
S
Ganso
M
M
Hildebrandt
C
C
Niebel
B
B
Spatz-Kümbel
G
G
Schmalzing
G
G
Mutschler
E
E
D000818:Animals; D005260:Female; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008297:Male; D058919:Purinergic P2 Receptor Antagonists; D011732:Pyridoxal Phosphate / Q000031:analogs & derivatives* / Q000494:pharmacology; D051381:Rats; D013451:Sulfonic Acids / Q000494:pharmacology*; D014981:Xenopus
D058919:Purinergic P2 Receptor Antagonists; D013451:Sulfonic Acids; C405633:pyridoxal-5'-phosphate-6-(2'-naphthylazo-6'-nitro-4',8'-disulfonate); C077792:pyridoxal phosphate-6-azophenyl-2',4'-disulfonic acid; D011732:Pyridoxal Phosphate