Ca2+ sensitization and the regulation of contractility in rat anococcygeus and retractor penis muscle

Cleber E. Teixeira, Liming Jin, Zhekang Ying, Trenis Palmer, R. Clinton Webb

Research output: Contribution to journalArticle

13 Scopus citations

Abstract

Stimulation of the RhoA/Rho-kinase (ROK) signaling represents a key step in the maintenance of agonist-induced contraction of smooth muscle. We aimed to demonstrate Ca2+ sensitization in rat anococcygeus and retractor penis muscles and to identify the molecular expression of major components of this pathway. Both anococcygeus and retractor penis showed a similar expression of RhoA, ROKα, and ROKβ at the protein level as well as the mRNA for RhoGEFs. Cumulative addition of the ROK inhibitors H-1152 (0.001-3 μM), Y-27632 (0.01-30 μM) or HA-1077 (0.01-30 μM) caused sustained relaxations of precontracted smooth muscle strips. Ca2+ sensitization induced by phenylephrine, norepinephrine and carbachol was markedly antagonized by all three ROK inhibitors. In addition, the contractile response to KCl-induced depolarization was highly sensitive to these ROK inhibitors. H-1152 was approximately 8-20 more potent than Y-27632 and HA-1077 to inhibit contraction. Electrical field stimulation (EFS, 1-32 Hz) caused transient contractions in both anococcygeus and retractor penis muscle, which were blocked by tetrodotoxin (1 μM), phentolamine (1 μM) or bretylium tosylate (30 μM). Similarly, H-1152 (0.1-1 μM), Y-27632 (1-10 μM) or HA-1077 (1-10 μM) significantly reduced EFS-evoked contractions in a concentration-dependent manner. The results indicate that the RhoA/ROK-mediated Ca2+ sensitization pathway is expressed in anococcygeus and retractor penis muscles and enhances contractions produced by receptor-dependent and independent mechanisms.

Original languageEnglish (US)
Pages (from-to)1483-1492
Number of pages10
JournalBiochemical Pharmacology
Volume69
Issue number10
DOIs
StatePublished - May 15 2005

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Keywords

  • Anococcygeus muscle
  • Ca sensitization
  • Retractor penis muscle
  • Rho-kinase
  • RhoA
  • RhoGEFs

ASJC Scopus subject areas

  • Biochemistry
  • Pharmacology

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