CLASSICAL NONCHOLINERGIC NEUROTRANSMITTERS AND THE VESICULAR TRANSPORT-SYSTEM FOR ACETYLCHOLINE

The acetylcholine transporter exhibits such low affinity and specifici ty for acetylcholine that it appeared possible it could fail to select against other neurotransmitters. Potential interactions of classical noncholinergic neurotransmitters with cholinergic synaptic vesicles pu rified from electric organ were studied. No active transport of [H-3]s erotonin, [H-3]noradrenaline, or [H-3]glutamate occurred. Serotonin, n oradrenaline, and N-acetylaspartyl glutamate inhibited active transpor t of [H-3]acetylcholine by the vesicles. Dopamine previously had been shown to inhibit transport. Glutamate and gamma-aminobutyric acid were shown here not to inhibit active transport of [H-3]-acetylcholine. No radrenaline was competitive with respect to [H-3]acetylcholine in this effect. Serotonin, noradrenaline, and dopamine inhibited binding of [ H-3]vesamicol to the vesicles, and dopamine was a competitive inhibito r of the binding of this allosteric ligand of the acetylcholine transp orter. The results indicate that the acetylcholine transporter does no t transport any other classical neurotransmitter, but serotonin, norad renaline, and dopamine bind to the acetylcholine site.