Effects of Ion Channel Blockers and Phorbol Ester Treatments on [3H]Dopamine Release and Neurotensin Facilitation of [3H]Dopamine Release from Rat Mesencephalic Cells in Primary Culture

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Abstract
In this work, we tested the effect of ion channel blockers and of phorbol ester treatments on [3H]dopamine ([3H]DA) release and neurotensin (NT)‐induced facilitation of [3H]DA release from cultures of rat fetal mesencephalic cells. The potassium channel blockers tetraethylammonium and 4‐aminopyridine increased basal [3H]DA release and decreased K+‐evoked [3H]DA release, whereas apamin was without effect. K+‐evoked [3H]DA release was decreased by ω‐conotoxin and nifedipine, totally suppressed by cadmium, and unaffected by amiloride. These results show the differential sensitivity of [3H]DA release to blockade of various ion channels and suggest the involvement of N‐type, L‐type, and non‐L‐non‐N‐type, but not T‐type, voltage‐sensitive calcium channels in K+‐evoked release. Phorbol 12‐myristate 13‐acetate increased both spontaneous and K+‐evoked [3H]DA release, suggesting a modulatory action of protein kinase C on DA release in this system. Unexpectedly, however, the effects of the phorbol ester were not counteracted by the protein kinase C inhibitors H7, staurosporine, or polymyxin B. NT‐induced facilitation of K+‐evoked [3H]DA release was insensitive to most of the ion channel blockers, except cadmium (64% decrease in NT effect), suggesting that the corresponding potassium' and calcium channels were not involved in the effect of NT on [3H]DA release in this system. The NT effect was totally suppressed by phorbol ester treatments, indicating a possible desensitization of the corresponding transduction mechanisms after protein kinase C activation.