Acetylcholine Synthesis and Release by a Sympathetic Ganglion in the Presence of 2‐(4‐Phenylpiperidino) Cyclohexanol (AH5183)

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Abstract
These experiments measured the release and the synthesis of acetylcholine (ACh) by cat sympathetic ganglia in the presence of 2-(4-phenylpiperidino) cyclohexanol (AH5183), an agent that blocks the uptake of ACh into synaptic vesicles. Evoked transmitter release during short periods of preganglionic nerve stimulation was not affected by AH5183, but release during prolonged stimulation was not maintained in the drug''s presence, whereas it was in the drug''s absence. The amount of ACh releasable by nerve impulses in the presence of AH5183 was 194 .+-. 10 pmol, which represented 14 .+-. 1% of the tissue ACh store. The effect of AH5183 on ACh release was not well antagonized by 4-aminopyridine (4-AP), and not associated with inhibition of stimulation-induced calcium accumulation by nerve terminals. It is concluded that AH5183 blocks ACh release indirectly, and that the proportion of stored ACh releasable in the compound''s presence represents transmitter in synaptic vesicles available to the release mechanism. The synthesis of ACh during 30 min preganglionic stimulation in the presence of AH5183 was 2,488 .+-. 51 pmol and in its absence it was 2,547 .+-. 273 pmol. Thus, as the drug decreased ACh release it increased tissue content. The increase in tissue content of ACh in the presence of AH5183 was not evident in resting ganglia; it was evident in stimulated ganglia whether or not tissue cholinesterase was inhibited; it was increased by 4-AP and reduced by divalent cation changes expected to decrease calcium influx during nerve terminal depolarization. It is concluded that increased ACh syntheis during activity can occur independent of transmitter release, and that the activation of nerve terminal ACh synthesis requires increased calcium influx.