Tyramine modulates synaptic transmission in vertebrate neuromuscular junction by releasing catecholamines and...

Tyramine is a biogenic amine whose role is closely linked to the sympathetic nervous system. Sympathetic axons densely innervate the neuromuscular junction regions of skeletal muscles. We hypothesized that tyramine might be the involvement in modulation of acetylcholine (ACh) release in the neuromuscular junctions. On the mouse Levator Auris Longus muscle it was found that tyramine enhances the loss of fluorescent false monoamine neurotransmitter FNN 511, preloaded into sympathetic varicosities located near the neuromuscular junctions. This indicates tyramine-induced release of endogenous catecholamines. Analysis of the ACh release demonstrated that tyramine decreases spontaneous exocytosis (estimated by the frequency of miniature endplate potentials) and evoked ACh secretion (assessed by the quantal content of the endplate potential). These inhibitory effects of tyramine were completely eliminated by doxazosin, an α1-adrenoreceptor blocker, but not SKF 86466, an α2-adrenoreceptor inhibitor. The negative action of tyramine on neuromuscular transmission was also manifested as a decrease in muscle contraction force during strong nerve activation. At the same time, tyramine did not inhibit the contractile responses to the direct muscle fiber stimulation. Finally, we obtained evidence of endogenous release of tyramine (and its derivative, octopamine) from the isolated neuromuscular preparation. Thus, tyramine can supress ACh release and, hence, contractile response to nerve activation probably by an indirect mechanism likely engaging the enhancement of endogenous catecholamine release and the downstream activation of α1-adrenoreceptors.