Release and effects of ATP and its derivatives at cholinergic synapses

ATP is released from many central and peripheral terminals in a rapid, synchronous manner. It can act both as a neurotransmitter substance and as a neuromodulator in conjunction with a primary neurotransmitter. We begin this perspective by reviewing the evidence for the quantal release of ATP together with acetylcholine (ACh) from motor nerve endings. Next, we discuss the inhibitory effects of adenosine derivatives on presynaptic and postsynaptic membranes at cholinergic synapses. With regard to the presynaptic effects of adenosine, after hydrolysis to adenosine ATP is the mediator of skeletal neuromuscular depression at low frequencies of stimulation. The evidence confirming the suggestion that this inhibitory effect of adenosine at motor nerve endings is mediated downstream of calcium entry is presented. Finally, the data showing the mutually occlusive effects of ATP and ACh at cholinoceptive neurons are summarized and discussed. Drug Dev. Res. 52:22–33, 2001. © 2001 Wiley‐Liss, Inc.