PROTECTION BY PHENTOLAMINE AGAINST THE EFFECTS OF PHENOXYBENZAMINE ON TRANSMITTER RELEASE ELICITED BY NERVE STIMULATION IN THE PERFUSED CAT HEART

Abstract

1 The effects of cocaine, phentolamine and phenoxybenzamine on neuronal uptake of [³H]-noradrenaline and on ³H-transmitter and noradrenaline overflow elicited by nerve stimulation were determined in the perfused heart of the cat. 2 During perfusion with cocaine 3.4 × 10⁻⁷m, there was a 2-fold increase in transmitter overflow while neuronal uptake of [³H]-noradrenaline was inhibited by 31.3 ± 2.1%. 3 After exposure to phenoxybenzamine 8.7 × 10⁻⁷m 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 [³H]-noradrenaline was inhibited by only 17.5 ± 5.4%. 4 There was no significant change in transmitter overflow or in neuronal uptake of [³H]-noradrenaline, 155 min after a 30 min exposure to phentolamine (3.2 × 10⁻⁵m). 5 Perfusion with phentolamine (3.2 × 10⁻⁵m) before and during exposure to phenoxybenzamine (8.7 × 10⁻⁷m), 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 α-adrenoceptors which regulate transmitter release through a negative feed-back mechanism.