AJP - Cell Physiology, Vol 269, Issue 4 C1018-C1024, Copyright © 1995 by American Physiological Society

ARTICLES

Protein kinase C in cyclic stretch-induced nerve growth factor production by urinary tract smooth muscle cells

K. Persson, J. J. Sando, J. B. Tuttle and W. D. Steers
Department of Urology, University of Virginia School of Medicine, Charlottesville 22908, USA.

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 (PDGF), 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 downregulate PKC. Western blot analysis confirmed partial downregulation of the Ca(2+)-dependent PKC-alpha and PKC-beta 1 and near complete downregulation of the Ca(2+)-independent PKC isozymes delta, epsilon, and zeta. 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.

This article has been cited by other articles:

				G. Apodaca Modulation of membrane traffic by mechanical stimuli Am J Physiol Renal Physiol, February 1, 2002; 282(2): F179 - F190. [Abstract] [Full Text] [PDF]

				Y. S. Edwards, L. M. Sutherland, and A. W. Murray NO protects alveolar type II cells from stretch-induced apoptosis. A novel role for macrophages in the lung Am J Physiol Lung Cell Mol Physiol, December 1, 2000; 279(6): L1236 - L1242. [Abstract] [Full Text] [PDF]

				U. C. Kopp, D. M. Farley, M. Z. Cicha, and L. A. Smith Activation of renal mechanosensitive neurons involves bradykinin, protein kinase C, PGE2, and substance P Am J Physiol Regulatory Integrative Comp Physiol, April 1, 2000; 278(4): R937 - R946. [Abstract] [Full Text] [PDF]

				P. B. Goforth, E. F. Ellis, and L. S. Satin Enhancement of AMPA-Mediated Current after Traumatic Injury in Cortical Neurons J. Neurosci., September 1, 1999; 19(17): 7367 - 7374. [Abstract] [Full Text] [PDF]

				H. S. Ennes, S. H. Young, J. A. Goliger, and E. A. Mayer Chemical signaling from colonic smooth muscle cells to DRG neurons in culture Am J Physiol Cell Physiol, March 1, 1999; 276(3): C602 - C610. [Abstract] [Full Text] [PDF]

				J. M. Park, J. G. Borer, M. R. Freeman, and C. A. Peters Stretch activates heparin-binding EGF-like growth factor expression in bladder smooth muscle cells Am J Physiol Cell Physiol, November 1, 1998; 275(5): C1247 - C1254. [Abstract] [Full Text] [PDF]

				D. B. Clemow, W. D. Steers, R. McCarty, and J. B. Tuttle Altered regulation of bladder nerve growth factor and neurally mediated hyperactive voiding Am J Physiol Regulatory Integrative Comp Physiol, October 1, 1998; 275(4): R1279 - R1286. [Abstract] [Full Text] [PDF]

				I. Suzuma, K. Suzuma, K. Ueki, Y. Hata, E. P. Feener, G. L. King, and L. P. Aiello Stretch-induced Retinal Vascular Endothelial Growth Factor Expression Is Mediated by Phosphatidylinositol 3-Kinase and Protein Kinase C (PKC)-zeta but Not by Stretch-induced ERK1/2, Akt, Ras, or Classical/Novel PKC Pathways J. Biol. Chem., January 4, 2002; 277(2): 1047 - 1057. [Abstract] [Full Text] [PDF]