title: NO modulates the apicolateral cytoskeleton of isolated hepatocytes by a PKC-dependent, cGMP-independent mechanism.
abstract: 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.
mesh_terms: D000818:Animals; D001692:Biological Transport; D002118:Calcium / Q000502:physiology; D002462:Cell Membrane / Q000502:physiology; D006152:Cyclic GMP / Q000502:physiology*; D003599:Cytoskeleton / Q000502:physiology*; D008099:Liver / Q000166:cytology / Q000502:physiology*; D008297:Male; D009569:Nitric Oxide / Q000502:physiology*; D010539:Permeability; D011493:Protein Kinase C / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D019108:Tight Junctions / Q000502:physiology
chemical_list: D009569:Nitric Oxide; D011493:Protein Kinase C; D006152:Cyclic GMP; D002118:Calcium