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Inhibition of Endogenous Acetylcholine Release by Blockade of Voltage-dependent Calcium Channels in Enteric Neurons of the Guinea-pig Colon
Authors:FRANCA MARINO  MANUELA MARCOLI  FABRIZIO DE PONTI  SERGIO LECCHINI  CARLO MARIA CASTELLETTI  GIAN MARIO FRIGO
Abstract:Abstract— The effects on acetylcholine release from the guinea-pig colon of the N-type calcium channel blocker ω-conotoxin GVIA (ω-conotoxin), the L-type calcium channel blocker nifedipine and the putative blocker of T-type channels, flunarizine, have been investigated. Endogenous basal acetylcholine release and electrically (1 Hz, 1 ms, 450 mA)-evoked overflow in the presence of cholinesterase inhibitor were studied. ω-Conotoxin (1–10 nM) and nifedipine (0·03–3 μm ) dose-dependently inhibited basal and electrically-evoked acetylcholine release. Maximal inhibition of basal or electrically-evoked acetylcholine release was about 40% for nifedipine and about 75% for ω-conotoxin. The potency of nifedipine was inversely related to the external calcium concentration: its EC50 value in low-calcium medium (0·5 Mm ) was as low as 12 Nm . Flunarizine inhibited acetylcholine release only at concentrations higher than 0·2 μm . Our results are consistent with an involvement of N- and L-type calcium channels in the control of the endogenous acetylcholine release from the guinea-pig colon.
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