Pattern recognition of amino acid signals partitions virtually all of the macaque retina into 16 separable biochemical theme classes, some further divisible by additional criteria. The photoreceptor→bipolar cell→ganglion cell pathway is composed of six separable theme classes, each possessing a characteristic glutamate signature. Neuronal aspartate and glutamine levels are always positively correlated with glutamate signals, implying that they largely represent glutamate precursor pools. Amacrine cells may be parsed into four glycine-dominated (including one glycine/GABA immunoreactive population) and four GABA-dominated populations. Horizontal cells in central retina possess a distinctive GABA signature, although their GABA content is constitutively lower than that of amacrine cells and shows both regional and sample variability. Finally, a taurine–glutamine signature defines Müller’s cells. We thus have established the fundamental biochemical signatures of the primate retina along with multiple metabolic subtypes for each neurochemical class and demonstrated that virtually all neuronal space can be accounted for by cells bearing characteristic glutamate, GABA, or glycine signatures.
Treatment of Neuro2a cells with drugs known to affect the integrity of microfilaments and microtubules, as well as with a calcium ionophore produced damage to the cellular membrane that was quantifiable by measuring the release of LDH into the culture medium. Concurrent exposure of the cells to ORG 2766 was found to modulate the release of LDH in a dose- and time-dependent fashion. ORG 2766 treatment was also able to reduce the basal release of LDH into the culture medium. [table: see text] The ORG 2766-induced reduction in LDH release was not due to down-regulation of protein synthesis. The peptide produced significant increases in protein synthesis relative to control conditions at concentrations of 10(-11) to 10(-6) M with 10(-8) M being an optimal dose. SDS-PAGE and 2-D PAGE analysis showed that de novo synthesis of most polypeptides was increased by about 40%. Additionally, a family of polypeptides tentatively identified as actins appear to undergo ORG 2766-dependent post translational charge modifications. These data are consistent with the hypothesis that regulation of transcription and/or translation are mechanisms important to the neurotrophic actions of ORG 2766.
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