Effect of chlorpromazine on PZ-peptidase and several other peptidase activities in cloned osteoblastic cells (MC3T3-E1).
The effect of chlorpromazine (CPZ) on the degradation of collagen and non-collagenous peptides in clonal osteoblastic MC3T3-E1 cells was investigated by measuring the activities of PZ-peptidase, collagenase-like peptidase (CL-peptidase), dipeptidyl-aminopeptidase (DAP), leucine aminopeptidase (LAP) (EC 3.4.11.1), and post-proline cleaving enzyme (PPCE) (EC 3.4.21.26). CPZ increased PZ-peptidase and CL-peptidase activities in a dose-related fashion, but it had no effect on LAP and PPCE activities in the cells. CPZ (10 micrograms/ml) enhanced the specific activities of PZ-peptidase, CL-peptidase, and DAP for 72 hr after the start of CPZ stimulation; in particular, about a 3.3-fold increase of PZ-peptidase activity was observed at 12 hr of culture. Furthermore, other phenothiazine derivatives specifically enhanced the PZ-peptidase, CL-peptidase, and DAP activities as well as CPZ. Since PZ-peptidase, CL-peptidase, and DAP, involved in the degradation of collagen peptides, were induced significantly by CPZ (and/or other phenothiazine derivatives) in comparison with LAP and PPCE, involved in the degradation of non-collagenous peptides, these results show that CPZ specifically stimulated collagen catabolism by inducing the collagen-catabolizing enzymes. In addition, CPZ specifically inhibited collagen synthesis in clonal osteoblasts.
Chikuma
T
T
Department of Pharmaceutical Analytical Chemistry, Showa College of Pharmaceutical Sciences, Tokyo, Japan.
Ishii
Y
Y
Kato
T
T
Kurihara
N
N
Hakeda
Y
Y
Kumegawa
M
M
D000626:Aminopeptidases / Q000378:metabolism; D000818:Animals; D002460:Cell Line; D002746:Chlorpromazine / Q000494:pharmacology*; D003094:Collagen / Q000096:biosynthesis*; D010450:Endopeptidases / Q000378:metabolism*; D008666:Metalloendopeptidases; D051379:Mice; D003012:Microbial Collagenase / Q000378:metabolism; D010006:Osteoblasts / Q000201:enzymology*; D010640:Phenothiazines / Q000494:pharmacology; D010643:Phenoxybenzamine / Q000494:pharmacology; D000085822:Prolyl Oligopeptidases; D011433:Propranolol / Q000494:pharmacology; D012697:Serine Endopeptidases / Q000378:metabolism
D010640:Phenothiazines; D010643:Phenoxybenzamine; D003094:Collagen; D011433:Propranolol; D010450:Endopeptidases; D000626:Aminopeptidases; D012697:Serine Endopeptidases; D000085822:Prolyl Oligopeptidases; D008666:Metalloendopeptidases; C022510:thimet oligopeptidase; D003012:Microbial Collagenase; D002746:Chlorpromazine