Regulation of endogenous dopamine release in amphibian retina by gamma-aminobutyric acid and glycine.
Endogenous dopamine release in the retina of the African clawed frog (Xenopus laevis) increases in light and decreases in darkness. The roles of the inhibitory amino acid transmitters gamma-aminobutyric acid (GABA) and glycine in regulating this light/dark difference in dopamine release were explored in the present study. Exogenous GABA, the GABA-A receptor agonist muscimol, the GABA-B receptor agonist baclofen, and the GABA-C receptor agonist cis-aminocrotonic acid (CACA) suppressed light-evoked dopamine overflow from eyecups. The effects of GABA-A and -B receptor agonists were selectively reversed by their respective receptor-specific antagonists, whereas the effect of CACA was reversed by the competitive GABA-A receptor antagonist bicuculline. The benzodiazepine diazepam enhanced the effect of muscimol on light-evoked dopamine release. Both GABA-A and -B receptor antagonists stimulated dopamine release in light or darkness. Bicuculline was more potent in light than in darkness. These data suggest that retinal dopaminergic neurons are inhibited by GABA-A and -B receptor activation in both light and darkness but that GABA-mediated inhibitory tone may be greater in darkness than in light. Exogenous glycine inhibited light-stimulated dopamine release in a concentration-dependent and strychnine-sensitive manner. However, strychnine alone did not increase dopamine release in light or darkness, nor did it augment bicuculline-stimulated release in darkness. Additionally, both strychnine and 7-chlorokynurenate, an antagonist of the strychnine-insensitive glycine-binding site of the N-methyl-D-aspartate subtype of glutamate receptor, suppressed light-evoked dopamine release. Thus, the role of endogenous glycine in the regulation of dopamine release remains unclear.
Boatright
J H
JH
Department of Pharmacology, Emory University School of Medicine, Atlanta, GA 30322-3090.
Rubim
N M
NM
Iuvone
P M
PM
D000818:Animals; D004298:Dopamine / Q000096:biosynthesis*; D004305:Dose-Response Relationship, Drug; D018755:GABA Agonists / Q000494:pharmacology; D005998:Glycine / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D008027:Light; D008297:Male; D012160:Retina / Q000187:drug effects / Q000378:metabolism*; D014982:Xenopus laevis; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology*
D018755:GABA Agonists; D005680:gamma-Aminobutyric Acid; D005998:Glycine; D004298:Dopamine