title: 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.
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 omega-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.
authors.affiliation: Institut National de la Santé et de la Recherche Médicale, Unité 339, Hôpital Saint-Antoine, Paris, France.
authors.forename: A
authors.initials: A
authors.lastname: Brouard
authors.forename: D
authors.initials: D
authors.lastname: Pelaprat
authors.forename: M
authors.initials: M
authors.lastname: Vial
authors.forename: A M
authors.initials: AM
authors.lastname: Lhiaubet
authors.forename: W
authors.initials: W
authors.lastname: Rostène
mesh_terms: D015761:4-Aminopyridine / Q000494:pharmacology; D000584:Amiloride / Q000494:pharmacology; D000818:Animals; D001030:Apamin / Q000494:pharmacology; D002478:Cells, Cultured; D004298:Dopamine / Q000378:metabolism*; D007473:Ion Channels / Q000187:drug effects / Q000502:physiology*; D008636:Mesencephalon / Q000196:embryology / Q000378:metabolism*; D009496:Neurotensin / Q000494:pharmacology*; D009543:Nifedipine / Q000494:pharmacology; D010455:Peptides / Q000494:pharmacology; D010703:Phorbol Esters / Q000494:pharmacology*; D011188:Potassium / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D019789:Tetraethylammonium; D013757:Tetraethylammonium Compounds / Q000494:pharmacology; D013779:Tetrodotoxin / Q000494:pharmacology; D014316:Tritium; D020866:omega-Conotoxin GVIA
chemical_list: D007473:Ion Channels; D010455:Peptides; D010703:Phorbol Esters; D013757:Tetraethylammonium Compounds; D014316:Tritium; D001030:Apamin; D009496:Neurotensin; D013779:Tetrodotoxin; D019789:Tetraethylammonium; D000584:Amiloride; D020866:omega-Conotoxin GVIA; D015761:4-Aminopyridine; D011493:Protein Kinase C; D009543:Nifedipine; D013755:Tetradecanoylphorbol Acetate; D011188:Potassium; D004298:Dopamine