The effect of kainate on protein kinase C, GABA, and the uptake of serotonin in the rabbit retina in vivo.
The purpose of this study was to investigate the effect of kainate on protein kinase C (PKC), gamma-aminobutyrate (GABA) and serotonin uptake in the rabbit retina. Kainate when injected into the vitreous humour produces a change in the GABA immunoreactivity within 6 hours. After 3 days, remnants of the normal GABA immunoreactivity still persist and additionally astrocyte and microglia-like elements "stain" positively for GABA. After 7 days exposure to kainate none of the normal GABA immunoreactivity is apparent, instead a number of round-shaped elements which may be reactive astrocytes and/or microglia stain positively for GABA. During these stages kainate does not affect the alpha PKC immunoreactivity associated with the on-bipolar cells. Six hours following kainate treatment the ability of certain GABA amacrine cells to take up exogenous serotonin is unaffected. After three days only a few of these cells can still take up exogenous serotonin and then not avidly. After seven days the GABA/serotonin amacrine cells cannot take up exogenous serotonin suggesting that all of these neurons are irreversibly damaged. One hour after treatment with kainate both calcium-dependent and -independent PKC species are translocated from the cytosolic to membrane compartments. After 5 hours and 7 days there was also evidence from the enzyme assay experiments that kainate caused the calcium-dependent and -independent PKC enzymes to be translocated but because the total enzyme activity was reduced due perhaps to down-regulation of the enzyme this was difficult to assess precisely.(ABSTRACT TRUNCATED AT 250 WORDS)
Osborne
N N
NN
Nuffield Laboratory of Ophthalmology, Oxford University, U.K.
McCord
R J
RJ
Wood
J
J
D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D004591:Electrophoresis, Polyacrylamide Gel; D015151:Immunoblotting; D007150:Immunohistochemistry; D007527:Isoenzymes / Q000302:isolation & purification / Q000378:metabolism; D007608:Kainic Acid / Q000494:pharmacology*; D007700:Kinetics; D011493:Protein Kinase C / Q000302:isolation & purification / Q000378:metabolism*; D011817:Rabbits; D012160:Retina / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D012701:Serotonin / Q000378:metabolism*; D013997:Time Factors; D014822:Vitreous Body / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D007527:Isoenzymes; D012701:Serotonin; D005680:gamma-Aminobutyric Acid; D011493:Protein Kinase C; D007608:Kainic Acid