Antagonism by the suramin analogue NF279 on human P2X(1) and P2X(7) receptors.
The effect of the suramin analogue 8,8'-(carbonylbis(imino-4, 1-phenylenecarbonylimino-4,1-phenylenecarbonylimino))bis(1,3 , 5-naphthalenetrisulfonic acid) (NF279) was analyzed on human P2X(1) and P2X(7) receptor subtypes (human P2X(1) and human P2X(7)) heterologously expressed in Xenopus oocytes using the two-microelectrode voltage-clamp technique. At activating ATP concentrations of 1 microM (human P2X(1)) and 10 microM ATP (human P2X(7)), IC(50) values of 0.05 microM and 2.8 microM were found for human P2X(1) and human P2X(7) receptors, respectively. An increase in the activating [ATP] shifted the NF279 concentration-inhibition curve rightwards for both receptors. NF279 slowed the activation of both human P2X(1) and human P2X(7) as well as the desensitization of human P2X(1). The data support a model in which desensitization of P2X(1) is dependent on preceding activation of these P2X receptors. It is concluded that NF279 acts as a competitive antagonist with much higher potency at human P2X(1) than at P2X(7) receptors. NF279 may hence be suited to discriminate between both receptors in native tissues.
Klapperstück
M
M
Julius-Bernstein-Institute for Physiology, Martin-Luther-University Halle, Magdeburger Strasse 6, D-06097, Halle, Germany.
Büttner
C
C
Nickel
P
P
Schmalzing
G
G
Lambrecht
G
G
Markwardt
F
F
D000818:Animals; D005260:Female; D006801:Humans; D058919:Purinergic P2 Receptor Antagonists; D013498:Suramin / Q000031:analogs & derivatives* / Q000494:pharmacology; D014982:Xenopus laevis
C114657:NF 279; D058919:Purinergic P2 Receptor Antagonists; D013498:Suramin