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Effect of cilnidipine, a novel dihydropyridine Ca++-channel antagonist, on N-type Ca++ channel in rat dorsal root ganglion neurons.

Authors
Type
Published Article
Journal
The Journal of pharmacology and experimental therapeutics
Publication Date
Volume
280
Issue
3
Pages
1184–1191
Identifiers
PMID: 9067302
Source
Medline
License
Unknown

Abstract

We investigated the effects of cilnidipine, a dihydropyridine derivative, on neuronal Ca++ channels in rat dorsal root ganglion neurons. Voltage-dependent Ca++-channel currents were recorded, using 5 mM Ba++ as the charge carrier, by means of the whole-cell patch-clamp technique. The Ba++ current was subdivided pharmacologically into calciseptine-sensitive (L-type), omega-conotoxin GVIA- (omegaCgTx) sensitive (N-type), omega-agatoxin IVA- (omegaAgTx) sensitive (P/Q-type) and toxin-resistant currents. Cilnidipine inhibited the L-type current with an IC50 of 100 nM in neurons pretreated with omegaCgTx plus omegaAgTx. In neurons pretreated with Cal plus omegaAgTx, cilnidipine induced a potent inhibition of the N-type current, but was unable to block the residual Ba++ current. The IC50 for cilnidipine in respect of the N-type current was 200 nM. Cilnidipine (300-500 nM) modified neither the voltage-dependent inactivation curve nor the decay of the N-type current. Furthermore, elevation of the holding potential did not enhance the inhibitory action of cilnidipine (300 nM) on the N-type current. No effect was induced by 100 nM cilnidipine on the P/Q-type current. However, nicardipine (1 microM) barely inhibited the N-type current at a concentration that almost completely blocked the L-type current. In conclusion, cilnidipine has potent inhibitory actions on N-type as well as L-type voltage-dependent Ca++-channel in rat dorsal root ganglion neurons. The former action may bestow an additional clinical advantage for the treatment of hypertension, such as suppression of reflex tachycardia.

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