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.
Hirai
K
K
Department of Autonomic Physiology, Tokyo Medical and Dental University, Japan. keijihirai.auto@und.ac.jp
Katayama
Y
Y
Misu
Y
Y
D000109:Acetylcholine / Q000378:metabolism*; D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002432:Cecum / Q000187:drug effects / Q000294:innervation; D002491:Central Nervous System Agents / Q000494:pharmacology*; D004594:Electrophysiology; D016257:Fura-2; D006168:Guinea Pigs; D066298:In Vitro Techniques; D007413:Intestinal Mucosa / Q000187:drug effects / Q000294:innervation / Q000378:metabolism*; D007980:Levodopa / Q000494:pharmacology*; D008297:Male; D008856:Microscopy, Fluorescence; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D010275:Parasympathetic Nervous System / Q000187:drug effects; D018408:Patch-Clamp Techniques; D011978:Receptors, Nicotinic / Q000187:drug effects; D017661:Receptors, Presynaptic / Q000187:drug effects / Q000378:metabolism*; D009435:Synaptic Transmission / Q000187:drug effects
D002491:Central Nervous System Agents; D011978:Receptors, Nicotinic; D017661:Receptors, Presynaptic; D007980:Levodopa; D000109:Acetylcholine; D002118:Calcium; D016257:Fura-2