Methoxyverapamil reduction of nicotine-induced catecholamine release involves inhibition of nicotinic acetylcholine receptor currents.
The mechanism by which the putative Ca2+ channel blocker methoxyverapamil (D600) inhibits nicotine-induced catecholamine release was investigated in bovine adrenal chromaffin cells and in neurons from paravertebral sympathetic ganglia of chick embryos. We found D600 to prevent catecholamine release evoked by 30 s applications of nicotine with a significantly higher potency than the release induced either by 30 s K+ depolarizations or by electrical field stimulation of sympathetic neurons. Like the use-dependent action of D600 upon Ca2+ channels, the magnitude of inhibition of the K(+)-evoked secretion depended on the duration of stimulation (10 s to 5 min). Data on catecholamine release were supplemented by patch-clamp recordings. We found whole-cell currents in chromaffin cells evoked by (extrapolated) 0.5 s applications of nicotine to be significantly more sensitive to D600 than Ca2+ currents induced 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 depolarizing) stimuli. Our data suggest that D600 inhibits nicotine-induced catecholamine release by reducing nicotinic acetylcholine receptor currents rather than voltage-gated Ca2+ currents. Hence, in chromaffin cells as well as in sympathetic neuronal preparations, D600 does not appear to be a suitable tool to investigate the part voltage-activated Ca2+ currents play in cellular events induced by nicotine.
Boehm
S
S
Department of Neuropharmacology, University of Vienna, Austria.
Huck
S
S
D000313:Adrenal Medulla / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D015220:Calcium Channels / Q000187:drug effects / Q000502:physiology*; D002417:Cattle; D002478:Cells, Cultured; D002642:Chick Embryo; D004558:Electric Stimulation; D005711:Gallopamil / Q000494:pharmacology*; D005728:Ganglia, Sympathetic / Q000378:metabolism*; D007700:Kinetics; D008564:Membrane Potentials / Q000187:drug effects; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D009538:Nicotine / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D009638:Norepinephrine / Q000378:metabolism*; D011978:Receptors, Nicotinic / Q000187:drug effects / Q000502:physiology*; D013997:Time Factors
D015220:Calcium Channels; D011978:Receptors, Nicotinic; D005711:Gallopamil; D009538:Nicotine; D009638:Norepinephrine