Homocholine and acetylhomocholine: False transmitters in the cholinergic electromotor system of Torpedo

Abstract

The subcellular distribution and acetylation of the choline analogue, N, N,N-trimethyl- N-3-hydroxypropylamine (homocholine) was studied using the electromotor system of Torpedo marmorata. Both choline and homocholine were transported into nerve terminals by the same high-affinity uptake mechanism (K T 2.0 and 3.5 μ m respectively), and became at least partly acetylated when blocks of electric tissue were perfused with [ 14C]choline and [ 3H]homocholine. Uptake of newly synthesized acetylcholine and acetylhomocholine into synaptic vesicles was enhanced by low-frequency stimulation of the block, and occurred into a metabolically active sub-fraction. Subsequent high frequency stimulation elicited the release of both 14C and 3H, in the same ratio as the two labels were isolated from the vesicle fraction. In other experiments it was shown that unacetylated homocholine was also released by stimulation, and found to be incorporated into vesicles in the same ratio to acetylhomocholine as it appeared in the perfusate. We conclude (a) that homocholine is not only a precursor to a cholinergic false transmitter (acetylhomocholine), but also qualifies as such, itself; (b) that uptake into vesicles under these conditions is not absolutely specific for acetylcholine and that prior acetylation is not an essential pre-requisite; and (c) that both acetylcholine and the two false transmitters are released from a vesicular compartment upon stimulation.