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Background
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Purotoxin1 (PT-1) is a peptide originally isolated from the Central Asian spider Geolycosa sp. It was shown to inhibit selectively P2X3 receptor channels at a 100 nM concentration. Studies were carried-out on cultured rat DRG neurons. Patch-clamp experiments did not show any inhibitory effect of PT-1 on voltage-gated channels (potentials range tested from -100 to 20 mV), neither on TRPV1 (after activation with 500 nM capsaicin). The selectivity of PT-1 for P2X3 was highlighted by activating this receptor with 10 μM ATP and 100 μM alpha, beta Methylene-ATP. Indeed, unlike P2X3, P2X2 and heterodimer P2X2/3 are known to be not sensitive to such concentrations. Moreover, P2X3, P2X2, and P2X2/3 are the only known ATP-sensitive receptors expressed in plasma membranes of DRG neurons. So, the observed effect seems to be well related to a selective inhibition of P2X3. P2X3-mediated current was fully inhibited with 100 nM PT-1, making it the most potent and selective ligand for P2X3.
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