Studies upon the mechanism by which acetylcholine releases surplus acetylcholine in a sympathetic ganglion.

1. Acetylcholine (ACh) releases surplus ACh from the superior cervical ganglion of the cat and the experiments described in this paper tested whether this results from exchange of endogenous ACh with exogenous ACh; the experiments also attempted to characterize pharmacologically the mechanism of this action of ACh. 2. The surplus ACh in the ganglion was radioactively labelled by perfusion of the ganglion with [3H]-choline-Krebs solution containing diisopropylphosphofluoridate, and the release of surplus [3H]-ACh by [14C]-ACh injected close arterially to the ganglion measured. The amount of [3H]-ACh released by [14C]-ACh was 33 +/- 5 times greater than was the amount of [14C]-ACh accumulated by ganglia. The amount of exogenous ACh accumulated by ganglia that had first formed surplus ACh was not different from exogenous ACh accumulation by ganglia that had not formed surplus ACh. Thus, it is concluded that surplus ACh release by ACh is not the result of ACh exchange. 3. In other experiments, surplus [3H]-ACh was accumulated in ganglia exposed to physostigmine. Nicotine, pilocarpine or ACh released surplus ACh; the effect of both nicotine and ACh was blocked by hexamethonium; atropine blocked the effect of ACh but not that of nicotine. It is concluded that both nicotinic and muscarinic receptors can be involved in the release of surplus ACh by cholinomimetic agonists.