Forskolin and isoproterenol effect discrete responses on epidermal growth factor induced DNA synthesis in aortic

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Updated: Sep 24, 2026

Drug-induced Sensitization of Adenylyl Cyclase: Assay Streamlining and Miniaturization for Small Molecule and siRNA Screening Applications
09:39

Drug-induced Sensitization of Adenylyl Cyclase: Assay Streamlining and Miniaturization for Small Molecule and siRNA Screening Applications

Published on: January 27, 2014

S L Venance1, B M Bennett, S C Pang

  • 1Department of Anatomy and Cell Biology, Queen's University, Kingston, ON, Canada.

Canadian Journal of Physiology and Pharmacology
|October 1, 1993
PubMed

Insights

Understanding vascular smooth muscle proliferation is key for atherosclerosis and hypertension research. Forskolin and isoproterenol show distinct effects on cell growth, suggesting a cyclic AMP-independent mechanism for isoproterenol

Area of Science:

  • Cardiovascular Biology
  • Cellular Physiology

Background:

  • Vascular smooth muscle cell (VSMC) proliferation is a critical factor in cardiovascular diseases like atherosclerosis and hypertension.
  • Understanding the regulatory mechanisms of VSMC proliferation is essential for developing targeted therapies.

Purpose of the Study:

  • To investigate the effects of forskolin and isoproterenol on cultured rat aortic smooth muscle cell proliferation.
  • To elucidate the role of cyclic AMP (cAMP) in mediating these effects.

Main Methods:

  • Primary rat aortic smooth muscle cells were cultured and treated with forskolin (adenylate cyclase activator) or isoproterenol (beta-adrenergic agonist).
  • Intracellular cAMP levels were measured.
  • DNA synthesis was assessed by [3H]thymidine incorporation following epidermal growth factor (EGF) stimulation.
  • Inhibition of phosphodiesterase with isobutylmethylxanthine (IBMX) was used to modulate cAMP levels.

Main Results:

  • Both forskolin and isoproterenol increased intracellular cAMP levels.
  • Forskolin and isoproterenol attenuated EGF-stimulated thymidine incorporation up to 12 hours post-stimulation.
  • After 16 hours, isoproterenol significantly enhanced thymidine incorporation by 50%, while forskolin continued to inhibit it by 40%.
  • These differential effects persisted despite homologous desensitization.

Conclusions:

  • Isoproterenol exhibits a biphasic effect on VSMC proliferation, with an early inhibitory phase and a later stimulatory phase.
  • The late stimulatory effect of isoproterenol on EGF-induced DNA synthesis appears to be independent of cyclic AMP.
  • These findings highlight complex signaling pathways regulating VSMC proliferation and offer potential therapeutic targets.

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