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Decreased phorbol ester binding in the parahippocampal gyrus from subjects with schizophrenia is not associated with changes in protein kinase C

Abstract

Combining in situ radioligand binding with autoradiography, we previously identified a reduction of [3H]phorbol 12,13-dibutyrate binding in the parahippocampal gyrus from schizophrenic subjects. To determine whether these changes were due to decreases in the level of protein kinase C, we measured [3H]phorbol 12,13-dibutyrate binding, levels of the protein kinase C isoforms α, β, δ, ε, γ, η and θ, as well as protein kinase C activity in crude particulate membranes from parahippocampal gyri of 15 schizophrenic and 15 control subjects. There was a significant decrease in the density (mean ± SEM: 6.56 ± 0.73 pmol mg−1 vs 9.68 ± 1.22 pmol mg−1; P < 0.05) and affinity (mean KD ± SEM: 4.64 ± 0.34 nM vs 2.95 ± 0.35 nM; P < 0.005) of [3H]phorbol 12,13-dibutyrate binding in homogenates from schizophrenic subjects. There were no significant changes in levels of the protein kinase C isoforms which are known to bind phorbol esters or in the activity of protein kinase C in membranes from schizophrenic subjects. These results suggest that there are changes in molecules capable of binding [3H]phorbol 12,13-dibutyrate, other than protein kinase C, in the parahippocampal gyrus from subjects with schizophrenia.

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Acknowledgements

The authors would like to acknowledge the invaluable assistance of the Victorian Institute of Forensic Medicine in the procurement of tissue for this study, as well as Christine Hill and Nicholas Keks for the diagnosis of schizophrenia. They would also like to thank both Andrew McKinnon and Paul Dudgeon for their valuable advice regarding statistical analyses.

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Correspondence to E Scarr.

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Scarr, E., Pavey, G., Robinson, P. et al. Decreased phorbol ester binding in the parahippocampal gyrus from subjects with schizophrenia is not associated with changes in protein kinase C. Mol Psychiatry 7, 683–688 (2002). https://doi.org/10.1038/sj.mp.4001065

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