Effects of a polyacetylene from Panax ginseng on Na+ currents in rat dorsal root ganglion neurons.
The root of ginseng (Panax ginseng) has been used as a traditional medicine in the far east countries since ancient times. Ginseng extracts produce analgesia among other various biologically beneficial effects. A polyacetylenic compound, (9R,10S)-epoxyheptadecan-4,6-diyn-3-one (EHD), has been isolated from ginseng extract, whose biological activity is largely unknown. Voltage-gated Na(+) channels in primary sensory neurons play important roles in pain perception. We investigated the effects of EHD on tetrodotoxin-sensitive (TTX-S) and tetrodotoxin-resistant (TTX-R) Na(+) currents in acutely dissociated rat dorsal root ganglion neurons. EHD inhibited both Na(+) currents in a concentration-dependent manner with an equal potency (K(d) values were both 14.3 microM). The activation voltage was not affected by EHD in either type of Na(+) current. However, EHD accelerated the inactivation of both Na(+) currents and produced a hyperpolarizing shift of the steady-state inactivation curve. In addition EHD suppressed the maximal Na(+) current at negative holding potentials at which the channels are relieved from inactivation. Thus EHD appears to bind both resting and inactivated channels. The recovery from inactivation of both Na(+) currents was also slowed by EHD. EHD inhibition of TTX-S Na(+) current but not TTX-R Na(+) current was frequency-dependent. This is the first report that a polyacetylene from ginseng inhibits Na(+) currents in primary sensory neurons. EHD by inhibiting Na(+) currents may contribute to the ginseng analgesia.
Choi
Sang Jin
SJ
Department of Pharmacology, Chung-Ang University, College of Medicine, 221 Heuksuk-Dong, Dongjak-Ku, Seoul 156-756, Republic of Korea.
Kim
Tae Hoon
TH
Shin
Yong Kyoo
YK
Lee
Chung Soo
CS
Park
Mijung
M
Lee
Hyun Sun
HS
Song
Jin-Ho
JH
D000114:Acetylene / Q000031:analogs & derivatives; D000480:Alkynes / Q000494:pharmacology*; D000818:Animals; D002478:Cells, Cultured; D004852:Epoxy Compounds / Q000494:pharmacology*; D005727:Ganglia, Spinal / Q000187:drug effects* / Q000378:metabolism; D008516:Medicine, Chinese Traditional; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009475:Neurons, Afferent / Q000187:drug effects* / Q000378:metabolism; D005894:Panax; D010936:Plant Extracts / Q000494:pharmacology*; D018517:Plant Roots; D053279:Polyynes / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015222:Sodium Channels / Q000187:drug effects* / Q000378:metabolism
C528871:9,10-epoxyheptadecan-4,6-diyn-3-one; D000480:Alkynes; D004852:Epoxy Compounds; D010936:Plant Extracts; D015222:Sodium Channels; D053279:Polyynes; D000114:Acetylene