Buthus martensi Karsch agonist of skeletal-muscle RyR-1, a scorpion active polypeptide: antinociceptive effect on rat peripheral nervous system and spinal cord, and inhibition of voltage-gated Na(+) currents in dorsal root ganglion neurons.

The antinociceptive effect and potential antinociceptive mechanism of Buthus martensi Karsch agonist of skeletal-muscle RyR-1 (BmK AS-1), a scorpion venom derived neurotoxic polypeptide, have been investigated in rats. The results show that: (a) the withdrawal latency to rat plantar radiant heat was increased significantly by 100 and 150% after intrathecal injection of 0.6 and 1.2 microg doses; (b) C components of rat nociceptive flexion reflex were reduced to 72, 50 and 29% after intraplantar injection of 5, 10 and 20 microg doses; (c) both central (spinal cord) and peripheral antinociceptive effects of BmK AS-1 could not be reversed by naloxone; (d) tetrodotoxin-resistant (TTX-R) Na(+) current was depressed to 83.87+/-1.64, 64.73+/-5.43 and 15.85+/-17.63%, and tetrodotoxin-sensitive (TTX-S) Na(+) current was depressed to about 81.27+/-2.5, 49.08+/-8.09 and 9.03+/-12.34% with 0.2, 1.0 and 10 microg/ml BmK AS-1 measured using patch clamp recording in rat small dorsal root ganglion (DRG) neurons, respectively. The results indicate that BmK AS-1 may be a new component with potent antinociceptive activity mediated by modulating TTX-S and TTX-R Na(+) channels.