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.
Tan
Z Y
ZY
Institute of Physiology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 200031, People's Republic of, Shanghai, China.
Mao
X
X
Xiao
H
H
Zhao
Z Q
ZQ
Ji
Y H
YH
D000818:Animals; D005727:Ganglia, Spinal / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D006358:Hot Temperature; D009119:Muscle Contraction / Q000502:physiology; D009475:Neurons, Afferent / Q000187:drug effects / Q000502:physiology; D009619:Nociceptors / Q000187:drug effects*; D010147:Pain Measurement / Q000187:drug effects; D018408:Patch-Clamp Techniques; D017933:Peripheral Nervous System / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D019837:Ryanodine Receptor Calcium Release Channel / Q000378:metabolism*; D012604:Scorpion Venoms / Q000494:pharmacology*; D015222:Sodium Channels / Q000378:metabolism*; D013116:Spinal Cord / Q000187:drug effects / Q000502:physiology; D013779:Tetrodotoxin / Q000494:pharmacology
C109066:KTX toxin, Buthus; D019837:Ryanodine Receptor Calcium Release Channel; D012604:Scorpion Venoms; D015222:Sodium Channels; D013779:Tetrodotoxin