Effect of chlorpromazine on pz-peptidase and several other peptidase activities in cloned osteoblastic cells (MC3T3-E1)

Toshiyuki Chikuma, Yoko Ishii, Takeshi Kato, Noriyoshi Kurihara, Yoshiyuki Hakeda, Masayoshi Kumegawa

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Abstract

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 μg/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.

Original languageEnglish (US)
Pages (from-to)4319-4324
Number of pages6
JournalBiochemical Pharmacology
Volume36
Issue number24
DOIs
StatePublished - Dec 15 1987

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ASJC Scopus subject areas

  • Biochemistry
  • Pharmacology

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