DOPA causes glutamate release and delayed neuron death by brain ischemia in rats.
DOPA seems to be a neuromodulator in striata and hippocampal CA1 and a neurotransmitter of the primary baroreceptor afferents terminating in the nucleus tractus solitarii (NTS) and baroreflex pathways in the caudal ventrolateral medulla and rostral ventrolateral medulla in the brainstem of rats. DOPA recognition sites differ from dopamine (DA) D(1) and D(2) and ionotropic glutamate receptors. Via DOPA sites, DOPA stereoselectively releases by itself neuronal glutamate from in vitro and in vivo striata. In the cultured neurons, DOPA and DA cause neuron death via autoxidation. In addition, DOPA causes autoxidation-irrelevant neuron death via glutamate release. Furthermore, DOPA released by four-vessel occlusion seems to be an upstream causal factor for glutamate release and resultant delayed neuron death by brain ischemia in striata and hippocampal CA1. Glutamate has been regarded as a neurotransmitter of baroreflex pathways. Herein, we propose a new pathway that DOPA is a neurotransmitter of the primary aortic depressor nerve and glutamate is that of secondary neurons in neuronal microcircuits of depressor sites in the NTS. DOPA seems to release unmeasurable, but functioning, endogenous glutamate from the secondary neurons via DOPA sites. A common following pathway may be ionotropic glutamate receptors-nNOS activation-NO production-baroreflex neurotransmission and delayed neuron death. However, we are concerned that DOPA therapy may accelerate neuronal degeneration process especially at progressive stages of Parkinson's disease.
Department of Pharmacology, Yokohama City University School of Medicine, Yokohama 236-0004, Japan. ymisu@zd5.so-net.ne.jp
Yoshimi
Y
Misu
Nobuya
N
Furukawa
Nobutaka
N
Arai
Takeaki
T
Miyamae
Yoshio
Y
Goshima
Kiyohide
K
Fujita
D000818:Animals; D002545:Brain Ischemia / Q000378:metabolism* / Q000503:physiopathology; D004295:Dihydroxyphenylalanine / Q000378:metabolism* / Q000633:toxicity; D018698:Glutamic Acid / Q000378:metabolism*; D009410:Nerve Degeneration / Q000378:metabolism* / Q000503:physiopathology; D009569:Nitric Oxide / Q000378:metabolism; D020734:Parkinsonian Disorders / Q000378:metabolism* / Q000503:physiopathology; D011311:Pressoreceptors / Q000166:cytology / Q000378:metabolism; D051381:Rats; D017552:Solitary Nucleus / Q000166:cytology / Q000378:metabolism; D017833:Visceral Afferents / Q000166:cytology / Q000378:metabolism
D009569:Nitric Oxide; D018698:Glutamic Acid; D004295:Dihydroxyphenylalanine