title: Modulation of P2X3 receptors by spider toxins.
abstract: Recently, the novel peptide named purotoxin-1 (PT1) has been identified in the venom of the spider Geolycosa sp. and shown to exert marked modulatory effects on P2X3 receptors in rat sensory neurons. Here we studied another polypeptide from the same spider venom, purotoxin-2 (PT2), and demonstrated that it also affected activity of mammalian P2X3 receptors. The murine and human P2X3 receptors were heterologously expressed in cells of the CHO line, and nucleotide-gated currents were stimulated by CTP and ATP, respectively. Both PT1 and PT2 negligibly affected P2X3-mediated currents elicited by brief pulses of the particular nucleotide. When subthreshold CTP or ATP was added to the bath to exert the high-affinity desensitization of P2X3 receptors, both spider toxins strongly enhanced the desensitizing action of the ambient nucleotides. At the concentration of 50nM, PT1 and PT2 elicited 3-4-fold decrease in the IC(50) dose of ambient CTP or ATP. In contrast, 100nM PT1 and PT2 negligibly affected nucleotide-gated currents mediated by mP2X2 receptors or mP2X2/mP2X3 heteromers. Altogether, our data point out that the PT1 and PT2 toxins specifically target the fast-desensitizing P2X3 receptor, thus representing a unique tool to manipulate its activity.
authors: Institute of Cell Biophysics, Russian Academy of Sciences, Pushchino, Moscow Region, Russia.
authors: Natalia V
authors: NV
authors: Kabanova
authors: Alexander A
authors: AA
authors: Vassilevski
authors: Olga A
authors: OA
authors: Rogachevskaja
authors: Marina F
authors: MF
authors: Bystrova
authors: Yuliya V
authors: YV
authors: Korolkova
authors: Kirill A
authors: KA
authors: Pluzhnikov
authors: Roman A
authors: RA
authors: Romanov
authors: Eugene V
authors: EV
authors: Grishin
authors: Stanislav S
authors: SS
authors: Kolesnikov
mesh_terms: D000818:Animals; D001483:Base Sequence; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D017931:DNA Primers; D013058:Mass Spectrometry; D016133:Polymerase Chain Reaction; D058477:Receptors, Purinergic P2X3 / Q000187:drug effects*; D013056:Spectrophotometry, Ultraviolet; D013111:Spider Venoms / Q000494:pharmacology*
chemical_list: D017931:DNA Primers; D058477:Receptors, Purinergic P2X3; D013111:Spider Venoms; C000620872:purotoxin-2, Alopecosa marikovskyi