AJP - Gastrointestinal and Liver Physiology, Vol 269, Issue 5 789-G799, Copyright © 1995 by American Physiological Society

ARTICLES

NO modulates the apicolateral cytoskeleton of isolated hepatocytes by a PKC-dependent, cGMP-independent mechanism

A. D. Burgstahler and M. H. Nathanson
Liver Study Unit, Yale University School of Medicine, New Haven, Connecticut 06520, USA.

Nitric oxide (NO) induces smooth muscle relaxation. We examined whether NO or its mediator of this action, guanosine 3',5'-cyclic monophosphate (cGMP), similarly induces relaxation of the apicolateral cytoskeleton in hepatocytes. Apical (canalicular) contractions were observed in isolated rat hepatocyte couplets by videomicroscopy, tight junction permeability was determined in the couplets by paracellular penetration of Texas red-dextran, and cytosolic Ca2+ (Ca2+i) was measured in isolated hepatocytes by fluorescence imaging. Unexpectedly, the NO donor sodium nitroprusside potentiated rather than inhibited apical contraction, in a cGMP-independent manner. This action of nitroprusside was blocked by hemoglobin or by inhibition of protein kinase C (PKC). Nitroprusside and 3-morpholinosydnonimine, another NO donor, each increased the permeability of hepatocyte tight junctions, a known effect of PKC in this cell type, and induced translocation of that kinase to the plasma membrane, as determined by immunocytochemistry. Neither nitroprusside nor dibutyryl cGMP changed the amplitude or frequency of Ca2+i signals in hepatocytes. Exogenous NO thus modulates the apicolateral cytoskeleton of hepatocytes via PKC activation rather than via cGMP or Ca2+i. These observations suggest a new role for NO: to activate PKC.

This article has been cited by other articles:

				X. Han, M. P. Fink, T. Uchiyama, R. Yang, and R. L. Delude Increased iNOS activity is essential for pulmonary epithelial tight junction dysfunction in endotoxemic mice Am J Physiol Lung Cell Mol Physiol, February 1, 2004; 286(2): L259 - L267. [Abstract] [Full Text] [PDF]

				K. S. Mark, A. R. Burroughs, R. C. Brown, J. D. Huber, and T. P. Davis Nitric oxide mediates hypoxia-induced changes in paracellular permeability of cerebral microvasculature Am J Physiol Heart Circ Physiol, January 1, 2004; 286(1): H174 - H180. [Abstract] [Full Text] [PDF]

				A. Mennone, A. S. Verkman, and J. L. Boyer Unimpaired osmotic water permeability and fluid secretion in bile duct epithelia of AQP1 null mice Am J Physiol Gastrointest Liver Physiol, September 1, 2002; 283(3): G739 - G746. [Abstract] [Full Text] [PDF]

				A. Mennone, D. Biemesderfer, D. Negoianu, C.-L. Yang, T. Abbiati, P. J. Schultheis, G. E. Shull, P. S. Aronson, and J. L. Boyer Role of sodium/hydrogen exchanger isoform NHE3 in fluid secretion and absorption in mouse and rat cholangiocytes Am J Physiol Gastrointest Liver Physiol, February 1, 2001; 280(2): G247 - G254. [Abstract] [Full Text] [PDF]

				M. Liang and F. G. Knox Nitric oxide activates PKCalpha and inhibits Na+-K+-ATPase in opossum kidney cells Am J Physiol Renal Physiol, December 1, 1999; 277(6): F859 - F865. [Abstract] [Full Text] [PDF]

				A. Huber, P. Trudrung, M. Storr, H. Franck, V. Schusdziarra, P. Ruth, and H.-D. Allescher Protein kinase G expression in the small intestine and functional importance for smooth muscle relaxation Am J Physiol Gastrointest Liver Physiol, October 1, 1998; 275(4): G629 - G637. [Abstract] [Full Text] [PDF]

				K. O. Aley, G. McCarter, and J. D. Levine Nitric Oxide Signaling in Pain and Nociceptor Sensitization in the Rat J. Neurosci., September 1, 1998; 18(17): 7008 - 7014. [Abstract] [Full Text] [PDF]

				T. A. Rooney, S. K. Joseph, C. Queen, and A. P. Thomas Cyclic GMP Induces Oscillatory Calcium Signals in Rat Hepatocytes J. Biol. Chem., August 16, 1996; 271(33): 19817 - 19825. [Abstract] [Full Text] [PDF]