Capsazepine block of voltage-activated calcium channels in adult rat dorsal root ganglion neurones in culture.
1. We have found that capsazepine, a competitive antagonist at the vanilloid (capsaicin) receptor, blocks voltage-activated calcium currents in sensory neurones. 2. The block of calcium current was slow to develop with a half time of about one minute at 100 microM and lasted for the duration of the experiment. The rate of block of calcium current was strongly concentration-dependent. 3. The EC50 for the blocking effect at 0 mV was 7.7 +/- 1.4 microM after 6 min exposure to capsazepine. The EC50 at equilibrium was estimated to be 1.4 +/- 0.2 microM. 4. The block of calcium current showed some voltage-dependence but there was no indication of any selectivity of action for a calcium channel subtype. The characteristics of the blocking action of capsazepine on the residual current of cells which were pretreated with either omega-conotoxin or nimodipine were similar to control. 5. The data suggest that capsazepine, in addition to its competitive antagonism of vanilloid receptors, has a non-specific blocking action on voltage-activated calcium channels which should be taken into account when interpreting the effects of this substance on intact preparations in vitro or in vivo.
Docherty
R J
RJ
Department of Pharmacology, United Medical and Dental Schools of Guy's and St Thomas', London.
Yeats
J C
JC
Piper
A S
AS
D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D015220:Calcium Channels / Q000187:drug effects*; D002211:Capsaicin / Q000031:analogs & derivatives* / Q000494:pharmacology; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D005260:Female; D005727:Ganglia, Spinal / Q000187:drug effects; D008297:Male; D010455:Peptides / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D020866:omega-Conotoxin GVIA
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D010455:Peptides; D020866:omega-Conotoxin GVIA; C071423:capsazepine; D002211:Capsaicin