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Characterization and distribution of glutathione receptors in primary visual cortex

Glutathione has been suggested to be one of the excitatory-amino-acid neurotransmitters in the brain (Ogita and Yoneda, 1987). We have attempted to characterize glutathione receptors in rat visual cortex and examine their distribution in rat, cat, and monkey primary visual cortex using in-vitro radioligand methods on 20-μm-thick cortex sections. Saturation binding of radiolabeled glutathione in rat primary occipital cortex sections revealed a high-affinity site (Kd = 5.4 nM; Bmax = 235 fmol/mg protein) and a denser lowaffinity site (Kd = 1.3 μM; Bmax = 1.3 pmol/mg protein), the latter in the affinity range for excitatory amino acid receptors. Kinetic and competition experiments yielded similar Kd values. Competition studies of the low-affinity glutathione binding site showed a separate site as well as binding with affinity for the neurotransmitter candidates cysteine, aspartate, and glutamate. Excitatory-amino-acid receptor subtype affinity was shown for AMPA. Radiolabeled glutathione binding in adult rat visual cortex showed a relatively uniform distribution across all cortical layers. The distribution of radiolabeled glutathione binding in cat area 17 was densest in layer 4 from 13 days postnatal to adult. Distribution in adult monkey area 17 showed a marked preference for layer 4C. Taken together with in-vivo evidence of uptake and possible retrograde transport of radiolabeled GSH and at least one of its constituent amino acids, cysteine, from terminals in area 17 into cell bodies in the lateral geniculate nucleus in rat (Arthur and Shaw, 1991), these data may suggest a role for glutathione as a geniculostriate neurotransmitter.