Protein kinase C-mediated modulation of glutamate transporter activity in rat retina.
It has previously been shown that inhibitors of protein kinase C (PKC) attenuate retinal glutamate uptake in situ. The aim of the current study was to determine whether PKCdelta-mediated inhibition differentially reduces the transport of glutamate into retinal Müller cells when compared with retinal neurons. The influence of two different types of PKC inhibitors on the uptake of [3H]D-aspartate was therefore compared in the intact retina, mixed retinal cultures, and Müller cell-enriched retinal cultures. It was found that 25 microM of the pan-isoform PKC inhibitor, chelerythrine, reduced [3H]D-aspartate uptake by 78%, 71%, and 68% in isolated retinas, mixed neuronal/glial cultures, and Müller cell-enriched cultures, respectively. Importantly, 20 microM of the PKCdelta-selective inhibitor rottlerin also reduced the uptake of D-aspartate to similar extents in all three systems, and the reductions were statistically similar to those found for the pan-specific PKC inhibitor. Neither pan-isoform nor PKCdelta-selective activators stimulated glutamate uptake in either culture system or the intact retina. The current results suggest that specific PKC inhibitors are quantitatively similar in reducing the uptake of glutamate into retinal neurons and Müller cells.
Bull
Natalie D
ND
Vision, Touch and Hearing Research Centre, School of Biomedical Sciences, University of Queensland, Brisbane, QLD 4072, Australia.
Wood
John P
JP
Osborne
Neville N
NN
Barnett
Nigel L
NL
D000098:Acetophenones / Q000494:pharmacology; D000470:Alkaloids / Q000494:pharmacology; D000818:Animals; D001224:Aspartic Acid / Q000378:metabolism; D053119:Benzophenanthridines / Q000494:pharmacology; D001578:Benzopyrans / Q000494:pharmacology; D018929:Cell Culture Techniques; D004791:Enzyme Inhibitors / Q000494:pharmacology; D027341:Excitatory Amino Acid Transporter 1 / Q000378:metabolism*; D018698:Glutamic Acid / Q000378:metabolism; D007124:Immunoenzyme Techniques; D009457:Neuroglia / Q000378:metabolism; D051745:Protein Kinase C-delta / Q000037:antagonists & inhibitors / Q000502:physiology*; D051381:Rats; D012160:Retina / Q000187:drug effects / Q000378:metabolism*
D000098:Acetophenones; D000470:Alkaloids; D053119:Benzophenanthridines; D001578:Benzopyrans; D004791:Enzyme Inhibitors; D027341:Excitatory Amino Acid Transporter 1; C493392:Slc1a3 protein, rat; D001224:Aspartic Acid; D018698:Glutamic Acid; C085746:rottlerin; C016299:chelerythrine; D051745:Protein Kinase C-delta