Glycine stimulates striatal dopamine release in conscious rats.
1. Glycine is an inhibitory neurotransmitter in the spinal cord and brainstem. The mechanism of this inhibition is via binding of glycine to specific receptors, increasing transmembrane Cl- conductance and hyperpolarizing neurones. Strychnine selectively antagonizes these effects. The role of glycinergic neurones in supraspinal regions is poorly understood. 2. Effects of glycine on release of catecholamines in the striatum were examined by microdialysis in freely-moving rats. Transcription of the genes encoding strychnine-sensitive glycine receptors was assessed in the striatum and substantia nigra, by use of reverse transcription followed by the polymerase chain reaction. 3. Glycine administered via the microdialysis probe dose-dependently increased concentrations of dopamine and its metabolites, dihydroxyphenylacetic acid and homovanillic acid, in the perfusate, indicating increased local release and metabolism of dopamine. Strychnine markedly attenuated these responses. Whereas striatal tissue did not contain mRNA for either the adult or neonatal form of strychnine-sensitive glycine receptor, nigral tissue contained a message for the adult form. 4. The results suggest that dopaminergic cells in the substantia nigra synthesize strychnine-sensitive glycine receptors and transport the receptors to terminals in the striatum. Occupation of the glycine receptors then exerts a net stimulatory effect on striatal dopamine release in vivo.
Yadid
G
G
Clinical Neuroscience Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892.
Pacak
K
K
Golomb
E
E
Harvey-White
J D
JD
Lieberman
D M
DM
Kopin
I J
IJ
Goldstein
D S
DS
D000818:Animals; D001483:Base Sequence; D002851:Chromatography, High Pressure Liquid; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism*; D017931:DNA Primers; D003956:Dialysis; D004298:Dopamine / Q000378:metabolism*; D005998:Glycine / Q000494:pharmacology*; D006719:Homovanillic Acid / Q000378:metabolism; D008297:Male; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D018009:Receptors, Glycine / Q000096:biosynthesis / Q000235:genetics; D013331:Strychnine / Q000494:pharmacology; D013378:Substantia Nigra / Q000378:metabolism; D014158:Transcription, Genetic
D017931:DNA Primers; D012333:RNA, Messenger; D018009:Receptors, Glycine; D013331:Strychnine; D005998:Glycine; D004298:Dopamine; D006719:Homovanillic Acid