Neurobiology of L-DOPAergic systems

Prog Neurobiol. 1996 Aug;49(5):415-54. doi: 10.1016/0301-0082(96)00025-1.

Abstract

L-DOPA is proposed to be a neurotransmitter and/or neuromodulator in CNS. It is released probably from neurons, which may contain L-DOPA as an end-product, and/or from some compartment other than catecholamine-containing vesicles. The L-DOPA itself produces presynaptic and postsynaptic responses. All are stereoselective and most are antagonized by competitive antagonist. In striatum, L-DOPA is neuromodulator, mother of catecholamines, not only a precursor for dopamine but also a potentiator of children for presynaptic beta-adrenoceptors to facilitate dopamine release and postsynaptic D2 receptors, and ACh release inhibitor. All may cooperate for Parkinson's disease. Meanwhile, supersensitization of increase in L-glutamate release to nanomolar levodopa was seen in Parkinson's model rats, which may relate to dyskinesia or "on-off" during chronic therapy. In lower brainstem, L-DOPA tonically activates postsynaptic depressor sites of NTS and CVLM and pressor sites of RVLM. L-DOPA is probably a neurotransmitter of primary baroreceptor afferents terminating in NTS. GABA, the inhibitory neuromodulator for baroreflex in NTS, tonically functions to inhibit, via GABAA receptors, L-DOPA release and depressor responses to levodopa. Levodopa inversely releases GABA. L-DOPAergic monosynaptic relay from NTS to CVLM and from PHN to RVLM is suggested. Tonic L-DOPAergic baroreceptor-aortic nerve-NTS-CVLM relay seems to carry baroreflex information. Disturbance of neuronal activity to release L-DOPA in NTS, loss of the activity in CVLM, enhancement of the activity with decreased decarboxylation and increase in sensitivity to levodopa in RVLM may be involved in maintenance of hypertension in SHR. This is a story of "L-DOPAergic receptors" with extremely high affinity and low density.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Afferent Pathways / physiology
  • Animals
  • Antiparkinson Agents / adverse effects
  • Antiparkinson Agents / therapeutic use
  • Brain Stem / physiopathology
  • Cardiovascular Physiological Phenomena
  • Central Nervous System / physiology*
  • Corpus Striatum / physiology
  • Disease Models, Animal
  • Humans
  • Hypothalamus / physiology
  • Levodopa / adverse effects
  • Levodopa / pharmacology
  • Levodopa / physiology*
  • Levodopa / therapeutic use
  • Models, Neurological
  • Motor Activity / physiology
  • Neurons / physiology
  • Neurotransmitter Agents / physiology
  • Parkinson Disease / physiopathology
  • Parkinson Disease, Secondary / physiopathology
  • Pressoreceptors / physiology
  • Rats
  • Rats, Inbred SHR
  • Rats, Inbred WKY
  • Receptors, Neurotransmitter / drug effects
  • Receptors, Neurotransmitter / physiology

Substances

  • Antiparkinson Agents
  • Neurotransmitter Agents
  • Receptors, Neurotransmitter
  • Levodopa