¹Division of Molecular Schizophrenia, The Mental Health Research Institute of Victoria, Parkville, Victoria, Australia

²Cell Signalling Unit, Children's Medical Research Institute, Wentworthville, NSW, Australia

Correspondence to: E Scarr, Division of Molecular Schizophrenia, The Mental Health Research Institute of Victoria, Locked Bag 11, Parkville, VIC 3052, Australia. E-mail: E.Scarr@papyrus. mhri.edu.au

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 , , , , , and , 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 K_D ± 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.

Molecular Psychiatry (2002) 7, 683-688. doi:10.1038/sj.mp.4001065

human; second messenger; postmortem; temporal lobe; mental illness