Selective inhibitor of P2X3 receptors

Purotoxin-1 (PT-1) is a peptide originally isolated from the Central Asian spider Geolycosa sp. Purotoxin-1 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 Purotoxin-1 for P2X3 was highlighted by activating this receptor with 10 µM ATP and 100 µM α, β 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 Purotoxin-1, making it the most potent and selective ligand for P2X3.

Therapeutic interest : pain

P2X3 receptors are known to be implicated in pain mechanisms. Behavioral experimentations carried-out on rat pain models using 0.5 nmol PT-1 injected intraplantar showed to reduce nociception. This anti-nociceptive effect is comparable to A-317491 compound (Abbott’s drug) with an amount of almost 3 orders of magnitude lower.

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Product code: N/A. Category: . Tags: , , .

AA sequence: Gly-Tyr-Cys3-Ala-Glu-Lys-Gly-Ile-Arg-Cys10-Asp-Asp-Ile-His-Cys15-Cys16-Thr-Gly-Leu-Lys-Cys21-Lys-Cys23-Asn-Ala-Ser-Gly-Tyr-Asn-Cys30-Val-Cys32-Arg-Lys-Lys-NH2
Disulfide bridges: Cys3-Cys16; Cys10-Cys21; Cys15-Cys32; Cys23-Cys30
Length (aa): 35
Formula: C155H248N50O48S8
Molecular weight: 3834.59 Da
Appearance: White lyophilized solid
Solubility: water and saline buffer
CAS number:
Source: Synthetic
Purity rate: > 97 %

Modulation of P2X3 receptors by spider toxins

Purinergic Membrane Receptors as Targets for the Effect of Purotoxin 1, a Component of Venom of Spiders from the Geolycosa Genus

Novel peptide from spider venom inhibits P2X3 receptors and inflammatory pain