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Role of rho kinase in the functional and dysfunctional tonic smooth muscles

Márcio A F de Godoy1, Satish Rattan

  • 1Department of Medicine, Division of Gastroenterology and Hepatology, Jefferson Medical College of Thomas Jefferson University, Philadelphia, PA, USA.

Trends in Pharmacological Sciences
|April 19, 2011
PubMed

Insights

Tonic smooth muscles generate myogenic tone via RhoA/ROCK II pathways, crucial in gastrointestinal and cardiovascular diseases. Targeting these pathways offers novel therapeutic strategies for these conditions.

Area of Science:

  • Physiology
  • Molecular Biology
  • Pharmacology

Background:

  • Tonic smooth muscles are vital in gastrointestinal and cardiovascular systems, differing from phasic muscles by spontaneous myogenic tone generation.
  • Myogenic tone is linked to neurohumoral substances and calcium sensitization, involving the Ras homolog gene family, member A (RhoA)/Rho-associated, coiled-coil containing protein kinase 2 (ROCK II) pathways.
  • Dysfunction in tonic smooth muscles contributes to serious gastrointestinal and cardiovascular diseases.

Purpose of the Study:

  • To elucidate the molecular pathways governing tonic smooth muscle myogenic properties.
  • To explore the roles of protein kinase C and the RhoA/ROCK II pathway in basal tone and disease pathophysiology.
  • To discuss potential novel therapeutic strategies targeting these pathways for gastrointestinal and cardiovascular diseases.

Main Methods:

  • Review of molecular signaling pathways in tonic smooth muscle.
  • Analysis of the contribution of RhoA/ROCK II and protein kinase C in myogenic tone.
  • Discussion of emerging therapeutic approaches, including RhoA/ROCK II inhibitors and RNA interference.

Main Results:

  • The RhoA/ROCK II pathway is a key contributor to basal tone and myogenic properties in tonic smooth muscles.
  • Protein kinase C also plays a role, with its interplay with RhoA/ROCK II influencing smooth muscle function.
  • Evidence suggests RhoA/ROCK II signaling is implicated in the pathophysiology of gastrointestinal and cardiovascular diseases.

Conclusions:

  • Understanding the RhoA/ROCK II pathway's role in tonic smooth muscle is critical for addressing related diseases.
  • Targeting RhoA/ROCK II activity presents a promising therapeutic avenue for gastrointestinal and cardiovascular disorders.
  • Further research into RhoA/ROCK II modulation could lead to effective treatments for debilitating conditions.

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