Protein kinase c involvement in cyclic stretch-induced nerve growth
factor production by urinary tract smooth muscle cells.
Persson, Katarina, Julianne J. Sando, Jeremy B. Tuttle, and William D.
Steers.
Departments of Urology, Pharmacology and Neuroscience, University
of Virginia School of Medicine, Charlottesville, Virginia, 22908,
USA
APStracts 2:0199C, 1995.
Cyclic stretch of cultured urinary tract smooth muscle cells has been
used to mimic some of the events that occur with bladder obstruction.
The stretch stimulus induces production of Nerve Growth Factor (NGF)
which has been implicated in changes in bladder innervation. Stretch
-induced NGF production was blocked by Actinomycin. Involvement of
Protein Kinase C (PKC) in the stretch-induced NGF production is
strongly suggested by the following observations. Phorbol ester
activators of PKC mimicked the stretch response as did Platelet
-Derived Growth Factor (PGDF) which acts, in part, through generation
of endogenous diacylglycerols. Both stretch- and PDGF-induced NGF
production were blocked by prolonged incubation with phorbol ester to
down regulate PKC. Western blot analysis confirmed partial down
regulation of the Ca2+-dependent PKC-[alpha] and PKC-[beta]I, and
near complete down regulation of the Ca2+-independent PKC isozymes
[delta], , and z. The involvement of PKC in transducing a physical
stimulus (stretch) into a biochemical response (NGF production) has
implications for novel types of therapeutic intervention in ailments
such as bladder obstruction.
Received 3 October 1994; accepted in final form 5 May 1995.
APS Manuscript Number C595-4.
Article publication pending Am. J. Physiol. (Cell Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 26 May 1995.