Voltage-sensitive Ca2+ channels in rat brain neocortical noradrenergic nerve terminals. Different sensitivity to inorganic and organic Ca2+ channel antagonists.
In rat cerebral cortex slices we investigated the Ca2+ dependency of noradrenaline release and the influence of inorganic and organic Ca2+ antagonists. Slices were preincubated with 3H-noradrenaline and then superfused with noradrenaline-free medium. Release of 3H-noradrenaline was elicited by electrical pulses. The stimulation-evoked release was dependent on the external Ca2+ concentration and was inhibited by Cd2+, Co2+ and Mg2+ in a concentration-related manner. These results indicate that electrically stimulated noradrenaline release depends on the Ca2+ influx after opening of voltage-sensitive Ca2+ channels. Organic Ca2+ antagonists were used in concentrations which had no major influence on the basal release rate. Of the drugs tested (bepridil, diltiazem, flunarizine, nimodipine, isradipine, prenylamine, verapamil) only flunarizine and nimodipine showed a minor inhibition of the stimulation-evoked release, which was less than 20% at 1 mumol/l. With nimodipine 10 mumol/l, there was a 6% facilitation of release. All other drugs except flunarizine and verapamil caused a slight facilitation of the stimulation-evoked release. The results provide evidence that the organic Ca2+ channel antagonists investigated do not or only minimally interfere with the noradrenergic nerve terminal Ca2+ channels in a tissue slice preparation. The release-facilitating effects of most organic Ca2+ antagonists cannot be interpreted by the present results.
Reimann
W
W
Gödecke Research Institute, Freiburg, FRG.
Köllhofer
U
U
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002413:Cations, Divalent / Q000494:pharmacology; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism*; D004558:Electric Stimulation; D066298:In Vitro Techniques; D007473:Ion Channels / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D009411:Nerve Endings / Q000187:drug effects / Q000378:metabolism; D009638:Norepinephrine / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains
D002121:Calcium Channel Blockers; D002413:Cations, Divalent; D007473:Ion Channels; D002118:Calcium; D009638:Norepinephrine