Endothelin-stimulated nitric oxide production in the isolated Kupffer cell.
Endothelin (ET) is a potent peptide mediator exhibiting a wide variety of effects in both the parenchymal and nonparenchymal hepatic cells. In the Kupffer cell, ET activates several transmembrane signaling pathways to generate numerous second messengers including the phospholipase C-generated products inositol-1,4,5-trisphosphate and diacylglycerol and the cyclooxygenase product prostaglandin E2 via specific ETB-type receptors. In addition to these findings, we have now demonstrated that endothelin stimulates the production of nitric oxide (NO) in the Kupffer cell in a time- and concentration-dependent manner. Western blot analysis indicates that ET-stimulated NO production occurs though activation of the inducible form of the nitric oxide synthase enzyme. These findings have important implications as the stimulation of NO production by ET may be part of the physiological response to inflammation or infection. Elevated levels of ET and NO have been found to be associated with numerous hepatic pathophysiological conditions that may contribute to derangements in the vascular system seen in these conditions.
Stephenson
K
K
Department of Surgery, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, Texas 78284, USA.
Gupta
A
A
Mustafa
S B
SB
Halff
G A
GA
D000818:Animals; D002118:Calcium / Q000494:pharmacology; D002614:Chelating Agents / Q000494:pharmacology; D004533:Egtazic Acid / Q000494:pharmacology; D019334:Endothelin-3 / Q000494:pharmacology*; D066298:In Vitro Techniques; D007700:Kinetics; D007728:Kupffer Cells / Q000187:drug effects* / Q000378:metabolism*; D008297:Male; D009569:Nitric Oxide / Q000096:biosynthesis*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D019323:omega-N-Methylarginine / Q000494:pharmacology
D002614:Chelating Agents; D019334:Endothelin-3; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D004533:Egtazic Acid; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D002118:Calcium