Ethyl analogues of homocholine : uptake, metabolism and releasability in the mammalian nervous system

The uptake, metabolism and releasability of ethyl-analogues of homocholine were studied in rat brain and cat superior cervical ganglion. Results from these experiments further describe the specificities of the processes of uptake and acetylation for choline and of storage and release for acetylcholine in the mammalian nervous system. Specificity at the level of the transport mechanism into synaptic vesicles in mammalian brain tissue was identified with acetyldiethylhomocholine, a poor substrate for vesicular compartmentation. This property of the analogue was exploited to study the site of origin of released transmitter from brain slices. When tissue was incubated with ('3)H choline and ('14)C diethylhomocholine, raising the concentration of K('+) caused increased release of ('3)H acetylcholine but not of ('14)C acetylated analogue; during rest, both compounds were released spontaneously. These results suggest that evoked transmitter release originates from the vesicular compartment and spontaneous release from the cytosol.Diethylhomocholine was also used to investigate the regulation of acetylcholine synthesis in the superior cervical ganglion of the cat. Treatments that affect accumulation and acetylation of choline and releasability of acetylcholine were tested for their effect on the accumulation and acetylation of diethylhomocholine. Results suggest that precursor delivery is important in regulating synthesis but that another factor, probably related to Ca('++) influx during nerve terminal impulse invasion, is also necessary