Effect of arvanil (N-arachidonoyl-vanillyl-amine), a nonpungent anandamide-capsaicin hybrid, on ion currents in NG108-15 neuronal cells.

Abstract

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.

• Authors: Yuk-Keung Lo, Hung-Ting Chiang, Sheng-Nan Wu
• Journal: Biochemical pharmacology (Biochem Pharmacol) Vol. 65 Issue 4 Pg. 581-91 (Feb 15 2003) ISSN: 0006-2952 [Print] England
• PMID: 12566085 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Arachidonic Acids
• Calcium Channels, L-Type
• Delayed Rectifier Potassium Channels
• Endocannabinoids
• Polyunsaturated Alkamides
• Potassium Channels
• Potassium Channels, Voltage-Gated
• arvanil
• capsinolol
• N-(4-O-glycerol-3-methoxybenzyl)nonivamide
• omega-Conotoxin GVIA
• Pertussis Toxin
• capsazepine
• Glycerol
• Capsaicin
• anandamide

Topics

• Action Potentials (drug effects)
• Animals
• Arachidonic Acids (pharmacology)
• Calcium Channels, L-Type (metabolism)
• Capsaicin (analogs & derivatives, pharmacology)
• Cell Line
• Delayed Rectifier Potassium Channels
• Drug Interactions
• Endocannabinoids
• Glycerol (analogs & derivatives, pharmacology)
• Hybrid Cells
• Mice
• Neurons (drug effects, metabolism, physiology)
• Pertussis Toxin (pharmacology)
• Polyunsaturated Alkamides
• Potassium Channels (metabolism)
• Potassium Channels, Voltage-Gated
• Rats
• omega-Conotoxin GVIA (pharmacology)