Two peptidase activities decrease in treated bipolar disorder not schizophrenic patients.
BACKGROUND
Inhibition of prolyl oligopeptidase (PO) in primary neuronal cultures has been shown to reverse the effect of the common mood-stabilizers lithium, valproic acid and carbamazepine. In clinical studies, abnormal plasma PO activity has been associated with bipolar disorder (BD) and schizophrenia. However, this association is complicated by the discovery in bovine plasma of a Z-Pro-prolinal-insensitive peptidase (ZIP), a novel enzyme that cleaves the same substrate as PO.


METHODS
We developed an assay to distinguish between ZIP and PO and measured both activities in plasma from 48 BD and 50 schizophrenic patients undergoing treatment and compared them with 50 control subjects.


RESULTS
ZIP activity is restricted to blood plasma, whereas PO activity is present in the cytosol of lymphocytes, but can also be detected in blood plasma. Significant decreases in their plasma activities were found between treated BD (p = 0.007 and 0.03 respectively) but not schizophrenic (p > 0.05) patients and controls.


CONCLUSIONS
We have found that the enzyme activity previously reported as plasma PO actually comprises two enzymes, PO and ZIP. This study shows a statistically significant decrease of both enzymes in BD patients undergoing lithium treatment. No statistically significant change in PO or ZIP activity is observed in schizophrenic patients.
Section of Molecular Genetics, Division of Psychological Medicine, Institute of Psychiatry, Kings College London, London, UK.
Gerome
G
Breen
Adrian J
AJ
Harwood
Kathryn
K
Gregory
Maggie
M
Sinclair
David
D
Collier
David
D
St Clair
Robin S B
RS
Williams
D014150:Antipsychotic Agents / Q000494:pharmacology* / Q000627:therapeutic use*; D001714:Bipolar Disorder / Q000097:blood / Q000188:drug therapy / Q000201:enzymology; D004151:Dipeptides / Q000037:antagonists & inhibitors* / Q000097:blood; D006801:Humans; D016651:Lithium Carbonate / Q000494:pharmacology* / Q000627:therapeutic use*; D009474:Neurons / Q000201:enzymology; D000085822:Prolyl Oligopeptidases; D012559:Schizophrenia / Q000097:blood / Q000188:drug therapy / Q000201:enzymology; D012697:Serine Endopeptidases / Q000097:blood / Q000378:metabolism*
D014150:Antipsychotic Agents; D004151:Dipeptides; D016651:Lithium Carbonate; C038541:N-benzyloxycarbonylprolylprolinal; D012697:Serine Endopeptidases; C000705287:PREPL protein, human; D000085822:Prolyl Oligopeptidases