Decreased phorbol ester binding in the parahippocampal gyrus from subjects with schizophrenia is not associated with changes in protein kinase C.
Combining in situ radioligand binding with autoradiography, we previously identified a reduction of [(3)H]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 [(3)H]phorbol 12,13-dibutyrate binding, levels of the protein kinase C isoforms alpha, beta, delta, epsilon, gamma, eta and theta, 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 [(3)H]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 [(3)H]phorbol 12,13-dibutyrate, other than protein kinase C, in the parahippocampal gyrus from subjects with schizophrenia.
Scarr
E
E
Division of Molecular Schizophrenia, The Mental Health Research Institute of Victoria, Parkville, Victoria, Australia. E.Scarr@papyrus.mhri.edu.au
Pavey
G
G
Robinson
P J
PJ
Opeskin
K
K
Copolov
D L
DL
Dean
B
B
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015153:Blotting, Western; D002273:Carcinogens / Q000378:metabolism / Q000494:pharmacology*; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008875:Middle Aged; D020534:Parahippocampal Gyrus / Q000378:metabolism*; D015240:Phorbol 12,13-Dibutyrate / Q000378:metabolism / Q000494:pharmacology*; D011493:Protein Kinase C / Q000378:metabolism; D011869:Radioligand Assay; D012559:Schizophrenia / Q000378:metabolism*; D015290:Second Messenger Systems / Q000502:physiology; D014316:Tritium
D002273:Carcinogens; D014316:Tritium; D015240:Phorbol 12,13-Dibutyrate; D011493:Protein Kinase C