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Practolol inhibits human skin fibroblast cell mat hydroxyproline accumulation
G R Elliott1, H E Amos, K Miller
1Department of Pharmacology, Faculty of Medicine, Erasmus University Rotterdam, The Netherlands.
Agents and Actions
|October 1, 1987
Summary
Practolol inhibits collagen synthesis in human skin fibroblasts by reducing hydroxyproline accumulation. This effect is concentration-dependent and observed in both normal and psoriasis-derived cells.
Area of Science:
- Pharmacology
- Dermatology
- Biochemistry
Background:
- Collagen synthesis is crucial for skin structure and integrity.
- Practolol is a beta-adrenergic blocker with potential effects on cellular processes.
- Understanding drug interactions with fibroblast collagen production is important for therapeutic applications.
Purpose of the Study:
- To investigate the effect of practolol on collagen synthesis in human skin fibroblasts in vitro.
- To determine the concentration-dependency and time-dependency of practolol's inhibitory action.
- To compare the effects of practolol, its metabolites, structural analogues, and related compounds on fibroblast collagen production.
Main Methods:
- Human skin fibroblasts (DT2PH) were cultured in vitro.
- Collagen synthesis was assessed by measuring hydroxyproline accumulation in the cell matrix.
- Practolol, its in vitro generated metabolites, and structural analogues were added to cell cultures at varying concentrations.
- Fibroblasts from uninvolved skin of a psoriasis patient (PS1) were used to assess differential sensitivity.
Main Results:
- Practolol significantly inhibited hydroxyproline accumulation in a concentration- and time-dependent manner (ID50 0.8 X 10(-3) M).
- Preinitiation of collagen synthesis or omission of ascorbic acid did not alter practolol's inhibitory effect.
- In vitro generated practolol metabolites and structural analogues showed no inhibitory effect.
- Propranolol and paracetamol also inhibited hydroxyproline levels.
- Psoriasis-derived fibroblasts (PS1) exhibited several-fold greater sensitivity to practolol and propranolol compared to normal skin fibroblasts.
Conclusions:
- Practolol effectively inhibits collagen synthesis in human skin fibroblasts in vitro.
- The inhibitory effect of practolol is not mediated by its known metabolites or structural analogues.
- Differential sensitivity to practolol and propranolol was observed between normal and psoriasis-derived fibroblasts, suggesting potential relevance in dermatological conditions.