Partial Bladder Outlet Obstruction Selectively Abolishes Protein Kinase C Induced Contraction of Rabbit Detrusor Smooth Muscle

Michaela C. Stanton, J. Christopher Austin, Daniel P. Delaney, Alex Gosfield, James O. Marx, Stephen A. Zderic, Samuel Chacko, Robert S. Moreland

Research output: Contribution to journalArticlepeer-review

9 Scopus citations

Abstract

Purpose: Despite the acute onset, partial bladder outlet obstruction in the rabbit induces detrusor remodeling similar to that in men with benign prostatic hyperplasia in terms of its impact on structural and functional alterations in smooth muscle. We determined if partial bladder outlet obstruction induced remodeling alters the protein kinase C signaling pathway that leads to contraction. Materials and Methods: Smooth muscle from control animals and those subjected to 2 weeks of partial bladder outlet obstruction were mounted for isometric force recording, measurement of myosin light chain phosphorylation and levels of adducin phosphorylation. Bladder muscle strips were stimulated by phorbol dibutyrate or carbachol in the presence and absence of bisindolylmaleimide-1. Results: Smooth muscle strips from animals subjected to partial bladder outlet obstruction showed little to no increase in stress in response to phorbol dibutyrate and no increase in myosin light chain phosphorylation levels. Muscle strips from control animals produced a robust contraction with concomitant increases in myosin light chain phosphorylation. Inhibition of protein kinase C by bisindolylmaleimide-1 significantly depressed carbachol induced contractions of muscle strips from control animals but it had no effect on carbachol induced contractions of muscle strips from outlet obstructed animals. Phorbol dibutyrate increased phospho-adducin levels in muscle strips from the 2 animal sources, suggesting that protein kinase C could be activated. Conclusions: We propose that partial bladder outlet obstruction does not alter protein kinase C activation, but rather abolishes or uncouples the pathway(s) downstream of protein kinase C, leading to contraction. Loss of this pathway may contribute to the loss of normal voiding behavior and the resultant decompensated state.

Original languageEnglish (US)
Pages (from-to)2716-2721
Number of pages6
JournalJournal of Urology
Volume176
Issue number6
DOIs
StatePublished - Dec 2006
Externally publishedYes

Keywords

  • bladder
  • bladder neck obstruction
  • myosin light chains
  • protein kinase C
  • rabbits

ASJC Scopus subject areas

  • Urology

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