Buthus martensi Karsch agonist of skeletal-muscle RyR-1, a scorpion activepolypeptide: 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 Buthu s martensi Karsch agonist of skeletal-muscle RyR-1 (BmK AS-1), a scorpion v enom derived neurotoxic polypeptide, have been investigated in rats. The re sults 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 mug doses; (b) C components of rat nociceptive flexion reflex were reduced to 72, 50 and 29% after intraplantar injection of 5, 10 and 20 mug doses; (c) both central (spinal cord) and peripheral antinociceptive effec ts of BmK AS-1 could not be reversed by naloxone; (d) tetrodotoxin-resistan t (TTX-R) Na+ current was depressed to 83.87 +/- 1.64, 64.73 +/- 5.43 and 1 5.85 +/- 17.63%, and tetrodotoxin-sensitive (TTX-S) Nai current was depress ed to about 81.27 +/- 2.5, 49.08 +/- 8.09 and 9.03 +/- 12.34% with 0.2, 1.0 and 10 mug/ml BmK AS-1 measured using patch clamp recording in rat small d orsal root ganglion (DRG) neurons, respectively. The results indicate that BmK AS-1 may be a new component with potent antinociceptive activity mediat ed by modulating TTX-S and TTX-R Na+ channels. (C) 2001 Elsevier Science Ir eland Ltd. All rights reserved.