Molecular basis of selective antagonism of the P2X1 receptor for ATP by NF449 and suramin: contribution of basic amino acids in the cysteine-rich loop.

ABSTRACT:

Background and purpose

The cysteine-rich head region, which is adjacent to the proposed ATP-binding pocket in the extracellular ligand-binding loop of P2X receptors for ATP, is absent in the antagonist-insensitive Dictyostelium receptors. In this study we have determined the contribution of the head region to the antagonist action of NF449 and suramin at the human P2X1 receptor.

Experimental approach

Chimeras and point mutations in the cysteine-rich head region were made between human P2X1 and P2X2 receptors. Mutant receptors were expressed in Xenopus oocytes and P2X receptor currents characterized using two-electrode voltage clamp.

Key results

The chimera replacing the region between the third and fourth conserved cysteine residues of the P2X1 receptor with the corre

SUBMITTER: El-Ajouz S 

PROVIDER: S-EPMC3268193 | biostudies-literature | 2012 Jan

REPOSITORIES: biostudies-literature