New research suggests it is highly probable that DOPA, in addition to being a precursor to dopamine, functions by itself as a neurotramsmitter and/or neuromodulator. Neurobiology of DOPA as a Neurotransmitter integrates background information about DOPA as an inert amino acid precursor of dopamine with the evidence showing that DOPA fulfills several criteria of neurotransmitters. Providing easy access to, and complete understanding of, the latest research on the subject, the book makes the case that DOPA meets many of the criteria of neurotransmitters and includes anti-evidence in some instances.
The book begins with a historical review of current knowledge of DOPA. It characterizes DOPA as a prominent example showing transmutation from an inert substance to a gold drug in Parkinson's disease and further to a neurotransmitter in its own right. The next chapters cover the essential criteria of a neurotransmitter such as synthesis, existence, and competitive antagonism. The book describes metabolism composed of catecholamine synthesis and degradation products related to neuron death, physiological release of DOPA in the lower brainstem, striatum, and nucleus accumbens, and physiological or pharmacological responses involved in baroreflex neurotransmission and related to behavioral science including interactions with catecholamines, acetylcholine, glutamate, and GABA. The book explores recognition sites, transport sites, and therapeutic role and mechanisms for neuron death related to adverse influence in the treatment of Parkinson's Disease.
Edited by experts in the field, the breadth and depth of information contained in this book is confirmed by a quick scan of the chapter authors. They summarize the issues surrounding DOPA neurotoxicity and explore the link between experimental studies and clinical relevance.
Table of Contents
L-DOPA: A Historical Perspective, O. Hornykiewicz
BIOSYNTHESIS, METABOLISM, ACTIVE TRANSPORT, AND EXISTENCE
DOPA as a Neurotransmitter Candidate, Y. Misu and Y. Goshima
Active Uptake System of L-DOPA in CNS, Y. Sasaki, Y. Goshima, and Y. Misu
Morphology of DOPAergic Neurons in Mammals, H. Okamura, T. Ueyama, S. Masubuchi, and K. Kitahama
Physiological Release of DOPA, Y. Misu, K. Honjo, and Y. Goshima
Mechanisms of Calcium-Associated Exocytosis of Striatal Dopamine and DOPA Release Studied by In Vivo Microdialysis, M. Okada, G. Zhu, S. Yoshida, S. Hirose, and S. Kaneko
Release of DOPA from Dog Peripheral Tissues, G.M. Tyce, L.W. Hunter, E.W. Kristensen, S.L. Chritton, and D.K. Rorie
Presynaptic Responses to Levodopa, Suggesting the Existence of DOPA Recognition Sites, Y. Goshima and Y. Misu
The Neuroregulatory Properties of Levodopa: Evidence and Potential Role in the Treatment of Parkinson's Disease, J. Tedroff
General Survey of Blood Pressure Regulation in Lower Brainstem and Responses to Levodopa and Glutamate, T. Kubo
Physiological and Pharmacological Responses to DOPA Involved in Baroreflex Neurotransmission in the Lower Brainstem of Anesthetized Rats, Y. Misu, K. Honjo, and Y. Goshima
Glutamatergic and Nitroxidergic Neurotransmission in the Nucleus Tractus Solitarii, W.T. Talman and L.-H. Lin
Is DOPA a Reliable Neurotransmitter of Baroreflex Neurotransmission in the Brainstem? M.-K. Sun
Levodopa Causes Increased Activity in Rats: The Clinical Implications, T. Nakazato
Behavioral Effects of Exogenously Applied and Endogenously Released DOPA, Y. Misu, K. Honjo, and Y. Goshima
Modulatory Effects of Levodopa on D2 Dopamine Receptors in Striatum Assessed Using In Vivo Microdialysis and PET, J. Opacka-Juffry and S.P. Hume
Dopamine-Independent Inhibition of Hippocampal CA1 Neurons Produced by Nanomolar Levodopa with Facilitation of Noradrenaline and GABA Release in Rats, M. Sasa, K. Ishihara, M. Akbar, and Y. Misu
Levodopa-Induced Vesicular Release of Glutamate and Mechanisms of Levodopa-Induced Neurotoxicity in Primary Neuron Cultures in Rat Striata, A. Akaike and T. Maeda
Neuroprotective and Neurotoxic Effects of L-DOPA in Rat Midbrain Dopaminergic Neurons in Culture, M. Angeles Mena, M.J. Casarejos, E. Rodríguez-Martín, R.M. Solano, J. Menéndez, and J. García de Yébenes
DOPA-an Upstream Factor for Glutamate Release and Delayed Neuron Death by Transient Ischemia in Striatum and Hippocampal CA1 Region of Conscious Rats, Y. Misu and Y. Goshima
Effect of Neonatal Treatment with Monosodium Glutamate on Dopamine and DOPA Neurons in the Medial Basal Hypothalamus of Rats, I. Bodnár, D. Szekács, M. Oláh, H. Okamura, M. Vecsernyés, M.I.K. Fekete, and G.M. Nagy
Molecular Mechanism of Memantine in Treatment of Alzheimer's Disease and Other Neurologic Insults, S.A. Lipton
"…a highly detailed review of antipsychotic drugs and neuroreceptors. There are many reviews of psychopharmacology, but this is one of the most specialized and exhaustive I have read. Any clinician or researcher interested in antipsychotic medications would find it a useful addition to their library."
-William Miles, M.D., Rush-Presbyterian-St. Luke's Medical Center
"The editors have succeeded well in their objective: to begin bridge the gap between the lab and the clinic. Dopamine, dopamine receptors, and dopamine transport lie at the core of important human disorders such as schizophrenia and Parkinson's disease. 4 Stars!"
- Daniel B. Hier, MD, University of Illinois at Chicago College of Medicine, for Doody's Review
"… present a timely overview of the different aspects of this amino acid in neurotransmission. … written by over 40 leading experts … a must-read for every neuroscientist working on endogenous neurotransmitters."
– Karl Gademann, Switzerland in ChemMedChem, 1, 2006