N-Ethyl analogues of choline as precursors to cholinergic false transmitters.

Abstract

Cat superior cervical ganglia perfused with the choline analogue, diethylcholine, acetylated the analogue and acetyldiethylcholine was subsequently released from the ganglia in response to preganglionic nerve stimulation by a Ca2+-dependent mechanism. Rat cerebral cortical slices incubated with monoethylcholine or diethylcholine acetylated the choline analogues, and both acetylmonoethylcholine and acetyldiethylcholine were released from the slices in response to stimulation by a high K+ concentration. In brain slices pre-incubated with monoethylcholine, diethylcholine, or triethylcholine, acetylated derivatives of the choline analogues were found in both free and bound nerve-ending stores, similar to the subcellular localization of [3H]acetylcholine (ACh) in brain slices pre-incubated with [3H]choline; the relative distribution of each of the acetylated choline analogues between the two nerve-ending stores differed only slightly from that of [3H]ACh. Nerve-ending free and bound stores of acetyldiethylcholine were equally depleted when brain slices were stimulated under conditions that cause depletion of releasable acetyldiethylcholine stores; similar results were obtained with acetyltriethylcholine. It is concluded that the three acetylated ethyl analogues of choline fulfill the necessary criteria for identification as cholinergic false transmitters, and that, under the conditions of the present experiments with brain, the false transmitters are able to distribute similarly to ACh between nerve-ending stores.