Smooth muscle caveolae differentially regulate specific agonist induced bladder contractions

V. Cristofaro, Craig A Peters, S. V. Yalla, Maryrose P. Sullivan

Research output: Contribution to journalArticle

33 Citations (Scopus)

Abstract

Aims: Caveolae are cholesterol-rich plasmalemmal microdomains that serve as sites for sequestration of signaling proteins and thus may facilitate, organize, and integrate responses to extracellular stimuli. While previous studies in the bladder have demonstrated alterations in caveolae with particular physiologic or pathologic conditions, little attention has been focused on the functional significance of these organelles. Therefore, the purpose of this study was to investigate the role of caveolae in the modulation of receptor-mediated signal transduction and determine the presence and localization of caveolin proteins in bladder tissue. Methods: Contractile responses to physiologic agonists were measured in rat bladder tissue before and after disruption of caveolae achieved by depleting membrane cholesterol with methyl-β-cyclodextrin. Stimulation with agonists was repeated after caveolae were restored as a result of cholesterol replenishment. RT-PCR, immmunohistochemistry, and Western blotting were used to determine the expression and localization of caveolin mRNA and proteins. Results: Following caveolae disruption, contractile responses to angiotensin II and serotonin were attenuated, whereas responses to bradykinin and phenylephrine were augmented. Cholesterol replenishment restored responses towards baseline. Carbachol and KCl induced contractions were not affected by caveolae disruption. Ultrastructure analysis confirmed loss of caveolae following cholesterol depletion with cyclodextrin and caveolae restoration following cholesterol replacement. Gene and protein expression of caveolin-1, -2, and -3 was detected in bladder tissue. Immunoreactivity for all three caveolins was observed in smooth muscle cells throughout the bladder. Conclusions: The functional effects of cholesterol depletion on specific agonist-induced contractile events and the expression of all three caveolins in bladder smooth muscle support a central role for caveolae in regulation of selective G-protein-coupled receptor signaling pathways in bladder smooth muscle. Thus, caveolae serve to differentially regulate bladder smooth muscle by a stimulus-dependent potentiation or inhibition of bladder contraction.

Original languageEnglish (US)
Pages (from-to)71-80
Number of pages10
JournalNeurourology and Urodynamics
Volume26
Issue number1
DOIs
StatePublished - Feb 2 2007

Fingerprint

Caveolae
Smooth Muscle
Urinary Bladder
Caveolins
Cholesterol
Cyclodextrins
Caveolin 2
Caveolin 1
Carbachol
Bradykinin
Phenylephrine
G-Protein-Coupled Receptors
Angiotensin II
Organelles
Smooth Muscle Myocytes
Signal Transduction
Serotonin
Proteins
Western Blotting

Keywords

  • Bladder
  • Caveolae
  • Smooth muscle

ASJC Scopus subject areas

  • Clinical Neurology
  • Urology

Cite this

Smooth muscle caveolae differentially regulate specific agonist induced bladder contractions. / Cristofaro, V.; Peters, Craig A; Yalla, S. V.; Sullivan, Maryrose P.

In: Neurourology and Urodynamics, Vol. 26, No. 1, 02.02.2007, p. 71-80.

Research output: Contribution to journalArticle

Cristofaro, V. ; Peters, Craig A ; Yalla, S. V. ; Sullivan, Maryrose P. / Smooth muscle caveolae differentially regulate specific agonist induced bladder contractions. In: Neurourology and Urodynamics. 2007 ; Vol. 26, No. 1. pp. 71-80.
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