The decrease of neuromuscular transmission by adenosine depends on previous neuromuscular depression.

The action of adenosine (0.5 mM) on neuromuscular transmission has been studied in the presence of progressively blocking concentrations of tubocurarine, tetrodotoxin, and high Mg2+/low Ca2+ solutions. Adenosine enhanced the inhibitory effects elicited either by tubocurarine (4 X 10(-7) - 12 X 10(-7) M), high Mg2+(5 - 11 mM) or low CA2+(0.8 - 0.3 mM) concentrations. The effect of adenosine depended upon the size of the previous neuromuscular inhibition. In the presence of tubocurarine, the inhibitory effects of adenosine were greater at room temperature than at 37 degrees C; however, adenosine was more potent at 37 degrees C than at room temperature in solutions with high Mg2+ or low Ca2+ concentrations. Adenosine did not change the inhibitory effects of tetrodotoxin either at 37 degrees C or at room temperature. These findings suggest that the partial neuromuscular blockade, for the inhibitory action of adenosine to be apparent, has to take place either postsynaptically via the blockade of ACh receptors or presynaptically at the nerve endings through a decrease in the evoked output of the transmitter. Since ATP and/or adenosine are released at the neuromuscular junction, a potential involvement of these substances in conditions with impairment of neuromuscular transmission (e.g. myasthenia gravis) is discussed.