Partial bladder outlet obstruction selectively abolishes protein kinase C induced contraction of rabbit detrusor smooth muscle.
OBJECTIVE
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.


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.
Stanton
Michaela C
MC
Department of Pharmacology and Physiology, Drexel University College of Medicine, 245 North 15th Street, Philadelphia, PA 19102, USA.
Austin
J Christopher
JC
Delaney
Daniel P
DP
Gosfield
Alex
A
Marx
James O
JO
Zderic
Stephen A
SA
Chacko
Samuel
S
Moreland
Robert S
RS
D000818:Animals; D004195:Disease Models, Animal; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000502:physiology*; D009130:Muscle, Smooth / Q000503:physiopathology*; D018994:Myosin Light Chains / Q000378:metabolism; D010766:Phosphorylation; D011493:Protein Kinase C / Q000502:physiology*; D011817:Rabbits; D001743:Urinary Bladder / Q000503:physiopathology; D001748:Urinary Bladder Neck Obstruction / Q000503:physiopathology*
D018994:Myosin Light Chains; D011493:Protein Kinase C