L-DOPA INDUCES CONCENTRATION-DEPENDENT FACILITATION AND INHIBITION OFPRESYNAPTIC ACETYLCHOLINE-RELEASE IN THE GUINEA-PIG SUBMUCOUS PLEXUS

Neurotransmitter- or neuromodulator-like actions of L-DOPA were invest igated with intracellular recordings from submucous plexus neurons of the guinea-pig caecum. L-DOPA at 30 nM augmented the amplitude of fast EPSPs, but did not affect depolarizations elicited by puff applicatio n of acetylcholine (ACh). The augmenting effect of L-DOPA on the fast EPSPs was counteracted by L-DOPA methyl eater. The fast EPSPs were dep ressed by 10 mu M L-DOPA, but transiently augmented after rinsing the drug. L-DOPA methyl ester did not affect the inhibitory, action of L-D OPA on the fast EPSPs, but antagonized the potentiation following the inhibition. The depolarization elicited by exogenously applied ACh was inhibited by 10 mu M L-DOPA. Intracellular Ca2+ concentrations ([Ca2](i)) of the neuronal soma were measured with fura-2 microfluorophotom etry. The transient increase in the [Ca2+](i) evoked by the somatic ac tion potential (Delta[Ca2+](AP)) was facilitated by 30 nM L-DOPA, but decreased by the drug at 10 mu M. It is concluded that L-DOPA at low c oncentrations enhances the Delta[Ca2+](AP), increasing the neurotransm itter release, but at high dose diminishes the Delta[Ca2+](AP), inhibi ting the neurotransmission.