Identification of regions of the P2X(7) receptor that contribute to human and rat species differences in antagonist effects.

ABSTRACT:

Background and purpose

Several P2X(7) receptor antagonists are allosteric inhibitors and exhibit species difference in potency. Furthermore, N(2)-(3,4-difluorophenyl)-N(1)-(2-methyl-5-(1-piperazinylmethyl)phenyl)glycinamide dihydrochloride (GW791343) exhibits negative allosteric effects at the human P2X(7) receptor but is a positive allosteric modulator of the rat P2X(7) receptor. In this study we have identified several regions of the P2X(7) receptor that contribute to the species differences in antagonist effects.

Experimental approach

Chimeric human-rat P2X(7) receptors were constructed with regions of the rat receptor being inserted into the human receptor. Antagonist effects at these receptors were measured in ethidium accumulation and radioligand binding studies.

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SUBMITTER: Michel AD 

PROVIDER: S-EPMC2584934 | biostudies-literature | 2008 Nov

REPOSITORIES: biostudies-literature