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Effect of cyclic AMP on cellular contractility and DNA synthesis in chorioretinal fibroblasts maintained in collagen
Abstract:
Dibutyryl cyclic AMP (db-cAMP), theophylline and forskolin were found to be potent inhibitors of DNA synthesis and cell contractility in chorioretinal fibroblasts maintained in 3-dimensional collagen matrices. Dose-response curves were constructed for the inhibitory action of these agents on both cellular parameters and their interrelationship examined by regression analysis. The results obtained indicate that these parameters were equally inhibited by cAMP with the exception of high concentrations of db-cAMP (greater than 10(-3) M) where a greater effect on DNA synthesis than cell contractility was observed which was attributed to additional inhibition of DNA synthesis by db-cAMP degradation products. It is proposed from the present results and those of other investigators that cAMP regulates non-transformed fibroblast proliferation and contraction through a common regulatory mechanism possibly involving cAMP-dependent protein kinases and calcium ions.
Insights
Cyclic AMP (cAMP) and its analogs effectively inhibit DNA synthesis and cell contraction in fibroblasts. This suggests a common regulatory mechanism for fibroblast proliferation and contraction involving cAMP.
Area of Science:
- Cell Biology
- Biochemistry
- Pharmacology
Background:
- Fibroblast function, including proliferation and contraction, is crucial in tissue development and repair.
- Cyclic AMP (cAMP) is a key second messenger involved in various cellular processes.
- Understanding the regulation of fibroblast behavior is important for therapeutic interventions.
Purpose of the Study:
- To investigate the inhibitory effects of cAMP-elevating agents on DNA synthesis and contractility in chorioretinal fibroblasts.
- To determine the dose-response relationship of these agents on cellular parameters.
- To explore the potential common regulatory mechanism of cAMP on fibroblast proliferation and contraction.
Main Methods:
- Culturing chorioretinal fibroblasts in 3-dimensional collagen matrices.
- Treating fibroblasts with dibutyryl cyclic AMP (db-cAMP), theophylline, and forskolin at various concentrations.
- Measuring DNA synthesis and cell contractility.
- Analyzing the interrelationship between inhibited parameters using regression analysis.
Main Results:
- Dibutyryl cyclic AMP (db-cAMP), theophylline, and forskolin potently inhibited both DNA synthesis and cell contractility.
- Dose-response curves revealed a consistent inhibitory effect across tested agents.
- At high concentrations, db-cAMP showed a more pronounced inhibition of DNA synthesis than contractility, potentially due to degradation products.
Conclusions:
- cAMP plays a significant role in regulating fibroblast proliferation and contraction.
- A common regulatory mechanism, possibly involving cAMP-dependent protein kinases and calcium ions, may govern these fibroblast functions.
- These findings contribute to understanding fibroblast behavior and potential therapeutic targets.