An electrophysiological analysis of the effects of amine-uptake blockers and alpha-adrenoceptor blockers on adrenergic neuromuscular transmission.

1 An electrophysiological study has been made of the effects of either blocking noradrenaline (NA) uptake or alpha-adrenoceptors on conduction in adrenergic preterminal axons and on NA release. 2 The excitatory junction potential (e.j.p.) evoked by a single stimulus increased slightly in duration (maximum 20%) in the presence of high concentrations of desipramine or cocaine (larger than or equal to 1 mug/ml) but there was no change in the spontaneous miniature excitatory junction potential (m.e.j.p.s); the single compound preterminal action potential was decreased in amplitude by a maximum of 10%. The e.j.p., m.e.j.p. and the terminal action potential were not altered by lower concentrations of these drugs (less than mug/ml). 3 The increased decline of the e.j.p. amplitude observed during the first few hundred impulses at high frequencies (10 Hz) in the presence of desipramine or cocaine was accompanied by a similar decline in the amplitude of the preterminal compound action potential, suggesting that the latter gave rise to the former. 4 These observations suggest that the action on post-synaptic alpha-adrenoceptors of NA released by single impulses is terminated by diffusion, and that any NA which is subsequently taken up into nerves is metabolized. 5 All the alpha-adrenoceptor blocking drugs tested reversed the normal depression in e.j.p. amplitude observed during the first few hundred impulses at high frequencies to facilitation; this was unaccompanied by any changes in the preterminal compound action potential. 6 Alpha-Adrenoceptor blocking drugs did not alter the potentiating effect which a conditioning impulse had on the amplitude of the e.j.p. evoked by a subsequent test impulse. The facilitated release of NA during trains of impulses was quantitatively predicted in terms of the addition of the individual potentiations introduced by each impulse in the train. 7 It is suggested that if there is an auto-inhibition of NA release, then it is unlikely that the pre- and post-synaptic alpha-adrenoceptors are identical.