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Protection by phentolamine against the effects of phenoxybenzamine on transmitter release elicited by nerve stimulation in the perfused cat heart
Authors:M B Farah  S Z Langer
Abstract:1 The effects of cocaine, phentolamine and phenoxybenzamine on neuronal uptake of (3)H]-noradrenaline and on (3)H-transmitter and noradrenaline overflow elicited by nerve stimulation were determined in the perfused heart of the cat.2 During perfusion with cocaine 3.4 x 10(-7)M, there was a 2-fold increase in transmitter overflow while neuronal uptake of (3)H]-noradrenaline was inhibited by 31.3 +/- 2.1%.3 After exposure to phenoxybenzamine 8.7 x 10(-7)M for 20 min and washing with drug-free solution for 165 min there was an 8-fold increase in transmitter overflow during nerve stimulation. Under these conditions neuronal uptake of (3)H]-noradrenaline was inhibited by only 17.5 +/- 5.4%.4 There was no significant change in transmitter overflow or in neuronal uptake of (3)H]-noradrenaline, 155 min after a 30 min exposure to phentolamine (3.2 x 10(-5)M).5 Perfusion with phentolamine (3.2 x 10(-5)M) before and during exposure to phenoxybenzamine (8.7 x 10(-7)M), prevented the increase in transmitter overflow observed after perfusion with phenoxybenzamine alone.6 Protection by phentolamine against the effects of phenoxybenzamine supports the view that the effects on transmitter release obtained after perfusion with phenoxybenzamine are due to the blockade of presynaptic alpha-adrenoceptors which regulate transmitter release through a negative feed-back mechanism.
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