Capsazepine block of voltage‐activated calcium channels in adult rat dorsal root ganglion neurones in culture

• Published in: British journal of pharmacology Vol. 121; no. 7; pp. 1461 - 1467
• Main Authors: Docherty, R J, Yeats, J C, Piper, A S
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01-08-1997; Nature Publishing
• Subjects: Animals; Biological and medical sciences; calcium antagonist; calcium channel; Calcium Channel Blockers - pharmacology; Calcium Channels - drug effects; calcium current; Capsaicin; Capsaicin - analogs & derivatives; Capsaicin - pharmacology; capsazepine; Cells, Cultured; Central nervous system; Central neurotransmission. Neuromudulation. Pathways and receptors; Dose-Response Relationship, Drug; Female; Fundamental and applied biological sciences. Psychology; Ganglia, Spinal - drug effects; Male; omega-Conotoxin GVIA; Peptides - pharmacology; Rats; Rats, Sprague-Dawley; Rats, Wistar; sensory neurone; Vertebrates: nervous system and sense organs; Spinal cord; Calcium; Rat; Capsaicin; Rodentia; Central nervous system; Electrophysiology; Posterior spinal root; Ionic channel; Ionic current; In vitro; Vertebrata; Biological fixation; Mammalia; Neuron; Adult animal; Primary culture; Antagonist; Mechanism of action; Biological receptor
• ISSN: 0007-1188; 1476-5381
• DOI: 10.1038/sj.bjp.0701272

We have found that capsazepine, a competitive antagonist at the vanilloid (capsaicin) receptor, blocks voltage‐activated calcium currents in sensory neurones.
The block of calcium current was slow to develop with a half time of about one minute at 100 μM and lasted for the duration of the experiment. The rate of block of calcium current was strongly concentration‐dependent.
The EC50 for the blocking effect at 0 mV was 7.7±1.4 μM after 6 min exposure to capsazepine. The EC50 at equilibrium was estimated to be 1.4±0.2 μM.
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.
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.