Effect of arvanil (N-arachidonoyl-vanillyl-amine), a nonpungent anandamide-capsaicin hybrid, on ion currents in NG108-15 neuronal cells.
The effects of arvanil (N-arachidonoyl-vanillyl-amine), a structural hybrid between capsaicin and anandamide, on ion currents in a mouse neuroblastoma and rat glioma hybrid cell line, NG108-15, were examined with the aid of the whole-cell voltage-clamp technique. Arvanil (0.2-50 microM) caused an inhibition of voltage-dependent L-type Ca(2+) current (I(Ca,L)) in a concentration-dependent manner. Arvanil produced no change in the overall shape of the current-voltage relationship of I(Ca,L). The IC(50) value of arvanil-induced inhibition of I(Ca,L) was 2 microM. Arvanil (5 microM) could shift the steady-state inactivation curve of I(Ca,L) to a more negative potential by approximately -15mV. No effect of arvanil (20 microM) on delayed rectifier K(+) current (I(K(DR))) was observed; however, capsaicin (20 microM), glyceryl nonivamide (20 microM) and capsinolol (20 microM) suppressed it significantly. Arvanil (20 microM) caused a slight reduction in the amplitude of erg (ether-à-go-go-related)-mediated K(+) current (I(K(erg))) without modifying the activation curve of this current, while capsaicin and glyceryl nonivamide were more effective in suppressing I(K(erg)). Under current-clamp configuration, arvanil decreased the firing frequency of action potentials. Arvanil-mediated inhibition of I(Ca,L) appeared to be independent of its binding to either vanilloid or cannabinoid receptors. The channel-blocking properties of arvanil may, at least in part, contribute to the underlying mechanisms by which it affects neuronal or neuroendocrine function.
Lo
Yuk-Keung
YK
Section of Neurology, Kaohsiung Veterans General Hospital, Kaohsiung City, Taiwan, ROC.
Chiang
Hung-Ting
HT
Wu
Sheng-Nan
SN
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D001095:Arachidonic Acids / Q000494:pharmacology; D020746:Calcium Channels, L-Type / Q000378:metabolism*; D002211:Capsaicin / Q000031:analogs & derivatives* / Q000494:pharmacology*; D002460:Cell Line; D051668:Delayed Rectifier Potassium Channels; D004347:Drug Interactions; D063388:Endocannabinoids; D005990:Glycerol / Q000031:analogs & derivatives* / Q000494:pharmacology; D006822:Hybrid Cells; D051379:Mice; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D037342:Pertussis Toxin / Q000494:pharmacology; D053284:Polyunsaturated Alkamides; D015221:Potassium Channels / Q000378:metabolism*; D024642:Potassium Channels, Voltage-Gated; D051381:Rats; D020866:omega-Conotoxin GVIA / Q000494:pharmacology
D001095:Arachidonic Acids; D020746:Calcium Channels, L-Type; D051668:Delayed Rectifier Potassium Channels; D063388:Endocannabinoids; D053284:Polyunsaturated Alkamides; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated; C121153:arvanil; C104667:capsinolol; C080418:N-(4-O-glycerol-3-methoxybenzyl)nonivamide; D020866:omega-Conotoxin GVIA; D037342:Pertussis Toxin; C071423:capsazepine; D005990:Glycerol; D002211:Capsaicin; C078814:anandamide