Evidence that transmitter can be released from regions of the nerve cell other than presynaptic axon terminal: axonal release of acetylcholine without modulation.

Release of acetylcholine from isolated preganglionic axons of sympathetic nerve trunk (cervical preganglionic sympathetic branch) of the cat was studied. In response to depolarization (KCl, 48.4 mM) acetylcholine was released into the eserinized Krebs solution. This release was shown to be dependent on extracellular Ca2+. Electrical stimulation (1 Hz) enhanced the release of acetylcholine from the isolated axonal preparation. The release by stimulation proved to be tetrodotoxin-sensitive and Ca2+-dependent. Evidence has been obtained that the acetylcholine released from sympathetic nerve trunks originates from the axon and not from Schwann cells: 5 days after section of the nerve, there was no release in response to stimulation. The release of acetylcholine from the axon is unlike that from axon terminals in that the rate of release cannot be enhanced by the inhibition of Na, K-adenosine 5'-triphosphatase (ouabain 2 X 10(-5) M) and cannot be modulated by noradrenaline (10(-6) M) or by morphine. Furthermore, although isolated nerve trunks took up [3H]choline by a hemicholinium-sensitive process, no radioactivity could be released upon electrical stimulation. It is suggested that the release of acetylcholine is not confined to axon terminals, but that it can be non-synaptically released by depolarization from axons provided Ca2+ is present.