The effect of calcium channel antagonists on the release of [3H]noradrenaline in the human neuroblastoma, SH-SY5Y.
The effect of calcium channel antagonists on depolarization and carbachol evoked release of [3H]noradrenaline in the human neuroblastoma, SH-SY5Y, was investigated. Nifedipine, verapamil and diltiazem completely inhibited the depolarization evoked release of [3H]noradrenaline with IC50 values of 0.44 +/- 0.1 microM, 3.6 +/- 0.24 microM and 5.6 +/- 0.2 microM respectively. In addition, nickel, cobalt and cadmium, all at 2 mM, inhibited depolarization evoked release by 89.2 +/- 2.3%, 72.6 +/- 1.6% and 102.5 +/- 1.4% respectively. Furthermore, omega-conotoxin resulted in at least 20% inhibition of potassium evoked release, suggesting a role of N-type calcium channels. Carbachol evoked release of [3H]noradrenaline was inhibited by 10(-4) M nifedipine, diltiazem and verapamil by 15.6 +/- 1.1%, 14.6 +/- 3.2% and 23.6 +/- 1.8% respectively and by 2 mM nickel, cobalt and cadmium by 13.8 +/- 3.2%, 34 +/- 2.1% and 6.5 +/- 3.7% respectively. These results suggest that depolarization evoked release of [3H]noradrenaline is mediated via L- and N-type calcium channels, whereas, carbachol evoked release does not appear to be coupled an L-, T- or N-type voltage sensitive calcium channel.
Murphy
N P
NP
Department of Cardiovascular Studies, University of Leeds, U.K.
Ball
S G
SG
Vaughan
P F
PF
D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002217:Carbachol / Q000494:pharmacology; D002413:Cations, Divalent / Q000494:pharmacology; D002460:Cell Line; D006801:Humans; D009423:Nervous System Neoplasms / Q000378:metabolism*; D009447:Neuroblastoma / Q000378:metabolism*; D009638:Norepinephrine / Q000378:metabolism*; D011188:Potassium / Q000378:metabolism / Q000494:pharmacology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D002121:Calcium Channel Blockers; D002413:Cations, Divalent; D002217:Carbachol; D013755:Tetradecanoylphorbol Acetate; D011188:Potassium; D009638:Norepinephrine