Does endogenous adenosine modulate the release of acetylcholine from motor nerve during single and repetitive...

In order to elucidate the physiological role of endogenous adenosine in regulating the release of acetylcholine, the effects of 8-phenyltheophylline, an antagonist of adenosine receptors and dipyridamole, an uptake inhibitor of adenosine, on the contractile response and quantal release of acetylcholine during single and repetitive stimulations of isolated mouse phrenic nerve-diaphragm preparations were studied. The curves relating the concentration vs. inhibition of contractile response to added adenosine and ATP were shifted parallel to the left by dipyridamole, but were shifted to the right by 8-phenyltheophylline at concentrations with little Ca2+-mobilization or phosphodiesterase inhibition. In the absence of exogenously added adenosine, 8-phenyltheophylline increased the quantal content of end-plate potentials (1 Hz), whereas dipyridamole decreased the quantal content. Successive decrease of the amplitude of end-plate potentials (e.p.p. run-down) evoked at 50 Hz was not changed either by 8-phenyltheophylline or by dipyridamole, suggesting that adenosine or ATP released from the motor nerve does not accumulate to an effective concentration even after repetitive stimulation for a feed-back regulation of the transmitter release. It is concluded that endogenous adenosine does inhibit the release of acetylcholine from motor nerve. However, the source of adenosine may be mostly from the muscle and is probably not involved in the feedback autoregulation.