olvanil and dihydrocapsaicin

Although capsaicin not only activates transient receptor potential vanilloid-1 (TRPV1) channels but also inhibits nerve conduction, the latter action has not yet been fully examined. The purpose of the present study was to know whether various vanilloids have an inhibitory action similar to that of capsaicin and further to compare their actions with that of local anesthetic procaine.. Fast-conducting compound action potentials (CAPs) were recorded from frog sciatic nerve fibers by using the air-gap method.. Capsaicin reversibly and concentration-dependently reduced the peak amplitude of the CAP. TRPV1 antagonist capsazepine did not affect the capsaicin activity, and powerful TRPV1 agonist resiniferatoxin had no effect on CAPs, indicating no involvement of TRPV1 channels. Capsaicin analogs and other various vanilloids also inhibited CAPs in a concentration-dependent manner. An efficacy sequence of these inhibitions was capsaicin=dihydrocapsaicin>capsiate>eugenol>guaiacol≥zingerone≥vanillin>vanillylamine. Vanillic acid had almost no effect on CAPs; olvanil and curcumin appeared to be effective less than capsaicin. Capsaicin and eugenol were, respectively, ten- and two-fold effective more than procaine in CAP inhibition, while each of guaiacol, zingerone and vanillin was five-fold effective less than procaine.. Various vanilloids exhibit CAP inhibition, the extent of which is determined by the property of the side chain bound to the vanillyl group, and some of them are more effective than procaine. These results may serve to unveil molecular mechanisms for capsaicin-induced conduction block and to develop antinociceptive drugs related to capsaicin.

Topics: Action Potentials; Animals; Antipruritics; Benzaldehydes; Benzylamines; Capsaicin; Curcumin; Diterpenes; Eugenol; Female; Guaiacol; Male; Procaine; Ranidae; Sciatic Nerve; Structure-Activity Relationship; TRPV Cation Channels; Vanillic Acid

Capsaicin (Cap) and its analogs (CAPanalogs) have diverse effects in sensory neurons including analgesia, implying they modulate other cellular targets besides the TRPV1 Cap receptor. Since Cap and CAPanalogs are not largely available and their chemical synthesis is cumbersome, they have been obtained through a direct lipase-catalyzed reaction. Capsiate, the ester CAPanalog, was synthesized using a novel enzymatic transacylation one-pot strategy. Five different CAPanalogs were synthesized by amidation in 2-methyl-2-butanol with higher yields than previously reported. Voltage-dependent Ca(2+) channels (Ca(v)s) are among the main Ca(2+) entry paths into cells. They are classified as high-voltage-activated Ca(2+) channels (HVA) and low-voltage-activated Ca(2+) channels (LVA) constituted only by T-type channels. Though HVA Ca(v)s are Cap sensitive, it is not known if capsaicinoids inhibit LVA Ca(v)s which participate in the primary sensory neuron pain pathway. Here we first report that Cap, dihydrocapsaicin, N-VAMC(8), N-VAMC(9), and N-VAMC(10) can directly and partially reversibly inhibit T-type Ca(v)s, whereas olvanil, capsiate, and vanillylamine cannot. The Cap inhibition of T-type Ca(v)s was independent of TRPV1 activation.

Topics: Animals; Calcium Channels, T-Type; Capsaicin; Cells, Cultured; Mice