L-DOPA induces concentration-dependent facilitation and inhibition of presynaptic acetylcholine release in the guinea-pig submucous plexus.

Neurotransmitter- or neuromodulator-like actions of L-DOPA were investigated 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 application of acetylcholine (ACh). The augmenting effect of L-DOPA on the fast EPSPs was counteracted by L-DOPA methyl ester. The fast EPSPs were depressed by 10 microM L-DOPA, but transiently augmented after rinsing the drug. L-DOPA methyl ester did not affect the inhibitory action of L-DOPA on the fast EPSPs, but antagonized the potentiation following the inhibition. The depolarization elicited by exogenously applied ACh was inhibited by 10 microM L-DOPA. Intracellular Ca2+ concentrations ([Ca2+]i) of the neuronal soma were measured with fura-2 microfluorophotometry. The transient increase in the [Ca2+]i evoked by the somatic action potential (delta[Ca2+]AP) was facilitated by 30 nM L-DOPA, but decreased by the drug at 10 microM. It is concluded that L-DOPA at low concentrations enhances the delta[Ca2+]AP, increasing the neurotransmitter release, but at high dose diminishes the delta[Ca2+]AP, inhibiting the neurotransmission.