Effects of ginsenosides, active components of ginseng, on nicotinic acetylcholine receptors expressed in Xenopus oocytes.
We investigated the effects of ginsenosides, the active ingredient of ginseng, on neuronal or muscle-type nicotinic acetylcholine receptor channel activity expressed in Xenopus oocytes after injection of cRNA encoding bovine neuronal alpha3beta4, alpha7 or human muscle alphabetadeltavarepsilon subunits. Treatment with acetylcholine elicited an inward peak current (I(ACh)) in oocytes expressing nicotinic acetylcholine receptor subtypes. Cotreatment with ginsenoside Rg2 and acetylcholine inhibited I(ACh) in oocytes expressing with alpha3beta4 or alphabetadeltavarepsilon but not in oocytes expressing alpha7 nicotinic acetylcholine receptors. The inhibition of I(ACh) by ginsenoside Rg2 was reversible and dose-dependent. The half-inhibitory concentrations (IC50) of ginsenoside Rg2 were 60.2+/-14.1 and 15.7+/-3.5 microM in oocytes expressing alpha3beta4 and alphabetadeltavarepsilon nicotinic acetylcholine receptors, respectively. The inhibition of I(ACh) by ginsenoside Rg2 was voltage-independent and noncompetitive. Other ginsenosides besides ginsenoside Rg2 also inhibited I(ACh) in oocytes expressing alpha3beta4 or alphabetadeltavarepsilon nicotinic acetylcholine receptors. The order of potency for the inhibition of I(ACh) was ginsenoside Rg2>Rf>Re>Rg1>Rc>Rb2>Rb1 in oocytes expressing alpha3beta4 nicotinic acetylcholine receptors and was ginsenoside Rg2>Rf>Rg1>Re>Rb1>Rc>Rb2 in oocytes expressing alphabetadeltavarepsilon nicotinic acetylcholine receptors. These results indicate that ginsenosides might regulate nicotinic acetylcholine receptors in a differential manner and this regulation might be one of the pharmacological actions of Panax ginseng.
Choi
Seok
S
National Research Laboratory for the Study of Ginseng Signal Transduction and Department of Physiology, College of Veterinary Medicine, Chonnam National University, Kwangju, South Korea.
Jung
Se Yeon
SY
Lee
Jun Ho
JH
Sala
Francisco
F
Criado
Manuel
M
Mulet
Jose
J
Valor
Luis Miguel
LM
Sala
Salvador
S
Engel
Andrew G
AG
Nah
Seung Yeol
SY
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D002417:Cattle; D004305:Dose-Response Relationship, Drug; D005260:Female; D015870:Gene Expression; D036145:Ginsenosides; D006801:Humans; D008564:Membrane Potentials / Q000187:drug effects; D009865:Oocytes / Q000187:drug effects / Q000378:metabolism; D005894:Panax / Q000737:chemistry*; D011978:Receptors, Nicotinic / Q000235:genetics / Q000502:physiology*; D012503:Saponins / Q000737:chemistry / Q000494:pharmacology*; D014982:Xenopus laevis
D036145:Ginsenosides; D011978:Receptors, Nicotinic; D012503:Saponins; D000109:Acetylcholine