METHOXYVERAPAMIL REDUCTION OF NICOTINE-INDUCED CATECHOLAMINE RELEASE INVOLVES INHIBITION OF NICOTINIC ACETYLCHOLINE-RECEPTOR CURRENTS

The mechanism by which the putative Ca2+ channel blocker methoxyverapa mil (D600) inhibits nicotine-induced catecholamine release was investi gated in bovine adrenal chromaffin cells and in neurons from paraverte bral sympathetic ganglia of chick embryos. We found D600 to prevent ca techolamine release evoked by 30 s applications of nicotine with a sig nificantly higher potency than the release induced either by 30 s K+ d epolarizations or by electrical field stimulation of sympathetic neuro ns. Like the use-dependent action of D600 upon Ca2+ channels, the magn itude of inhibition of the K+-evoked secretion depended on the duratio n of stimulation (10 s to 5 min). Data on catecholamine release were s upplemented by patch-clamp recordings. We found whole-cell currents in chromaffin cells evoked by (extrapolated) 0.5 s applications of nicot ine to be significantly more sensitive to D600 than Ca2+ currents indu ced by a 0.5 s depolarization from -80 to 0 mV. In both instances, the potency of D600 depended on the duration of the (nicotinic and depola rizing) stimuli. Our data suggest that D600 inhibits nicotine-induced catecholamine release by reducing nicotinic acetylcholine receptor cur rents rather than voltage-gated Ca2+ currents. Hence, in chromaffin ce lls as well as in sympathetic neuronal preparations, D600 does not app ear to be a suitable tool to investigate the part voltage-activated Ca 2+ currents play in cellular events induced by nicotine.