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Adrenoceptor activators and blockers are widely used clinically for the treatment of cardiovascular and pulmonary disorders. More recently, adrenergic agents have also been used to treat neurodegenerative diseases. Recent studies indicate a location of sympathetic varicosities in close proximity to neuromuscular junctions. The pressing question is whether there could be any effects of endo- or exogenous catecholamines on cholinergic neuromuscular transmission. It was shown that the pharmacological stimulation of adrenoceptors, as well as sympathectomy, can affect both acetylcholine release from motor nerve terminals and the functioning of postsynaptic acetylcholine receptors. In this review, we discuss the recent data regarding the effects of adrenergic drugs on neurotransmission at the neuromuscular junction. The elucidation of the molecular mechanisms by which the clinically relevant adrenomimetics and adrenoblockers regulate quantal acetylcholine release from the presynaptic nerve terminals and postsynaptic sensitivity may help in the design of highly effective and well-tolerated sympathomimetics for treating a number of neurodegenerative diseases accompanied by synaptic defects.

The effects of high-frequency nerve stimulation (10-100 Hz) on the kinetics of evoked acetylcholine quanta secretion from frog motor nerve endings were studied. The amplitude and temporal parameters of uni-and multiquantal endplate currents were analysed to estimate the possible changes in the degree of synchrony of quantal release. The frog neuromuscular synapse is unusually long and we have placed special emphasis on evaluating the velocity of propagation of excitation along the nonmyelinated nerve ending as this might influence the synchrony of release from the whole terminal and hence affect the time course of postsynaptic currents. The data show that high-frequency firing leads to the desynchronization of acetylcholine release from motor nerve endings governed by at least two independent factors, namely a reduction of nerve pulse propagation velocity in the nonmyelinated parts of the axon and a change of secretion kinetics at single active zones. A computer reconstruction of the multiquantal synaptic response was performed to estimate any contribution of each of the above factors to the total rate of release and amplitude and time characteristics of the endplate currents. The results indicate that modification of the kinetics of neurotransmitter quanta release during high-frequency firing should be taken into account when mechanisms underlying the plasticity of chemical synapses are under investigation.

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There is some evidence that glutamate (Glu) acts as a signaling molecule at vertebrate neuromuscular junctions where acetylcholine (ACh) serves as a neurotransmitter. In this study, performed on the cutaneous pectoris muscle of the frog Rana ridibunda, Glu receptor mechanisms that modulate ACh release processes were analyzed. Electrophysiological experiments showed that Glu reduces both spontaneous and evoked quantal secretion of ACh and synchronizes its release in response to electrical stimulation. Quisqualate, an agonist of ionotropic α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic receptors and metabotropic Group I mGlu receptors, also exerted Glu-like inhibitory effects on the secretion of ACh but had no effect on the kinetics of quantal release. Quisqualate's inhibitory effect did not occur when a blocker of Group I mGlu receptors (LY 367385) or an inhibitor of phospholipase C (U73122) was present. An increase in the degree of synchrony of ACh quantal release, such as that produced by Glu, was obtained after application of N-methyl-D-aspartic acid (NMDA). The presence of Group I mGlu and NMDA receptors in the neuromuscular synapse was confirmed by immunocytochemistry. Thus, the data suggest that both metabotropic Group I mGlu receptors and ionotropic NMDA receptors are present at the neuromuscular synapse of amphibians, and that the activation of these receptors initiates different mechanisms for the regulation of ACh release from motor nerve terminals. © 2016 Wiley Periodicals, Inc.

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