The role of prostaglandins in triggering the liver regeneration cascade.
Following injury or surgical resection, the liver has the remarkable ability to regenerate. Despite over 100 years of research, the trigger of the liver regeneration cascade has only recently been identified. Shear stress-induced nitric oxide (NO), released secondary to a hemodynamic event following partial hepatectomy (PHX), has been implicated as the trigger of the liver regeneration cascade. However, it is also known that prostaglandins (PGs) are released following PHX, and in response to shear stress. Therefore, it is hypothesized that PGs, released secondary to an increase in the blood flow-to-liver mass ratio following PHX, trigger the liver regeneration cascade, and that NO and PGs interact during the triggering event. An index of initiation of the liver regeneration cascade, c-fos mRNA expression 15 min after PHX, has been employed. As expected, c-fos mRNA expression increased 15 min after PHX and this increase was inhibited by the NO synthase antagonist, l-NAME. This inhibition was reversed by the NO donors, SIN-1 and SNAP, and by the PGs, PGE2 and PGI2. Also, the increase in c-fos mRNA expression was inhibited by indomethacin, a cyclooxygenase antagonist. This inhibition was also reversed by the NO donors, SIN-1 and SNAP, and by the PGs, PGE2 and PGI2. These results suggest that there is interaction between NO and PGs in triggering the liver regeneration cascade, and that in a situation where either NO or COX is inhibited, provision of excess exogenous NO or PGs can reverse the inhibition. This suggests that exogenous NO and/or PGs may play a role in potentiation of the liver regeneration cascade.
Schoen Smith
Jodi M
JM
Department of Pharmacology and Therapeutics, Faculty of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada R3E 0T6.
Lautt
W Wayne
WW
D000818:Animals; D004347:Drug Interactions; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006498:Hepatectomy; D008115:Liver Regeneration; D008297:Male; D009569:Nitric Oxide / Q000502:physiology; D020030:Nitric Oxide Donors / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D011453:Prostaglandins / Q000502:physiology*; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley
D004791:Enzyme Inhibitors; D020030:Nitric Oxide Donors; D011453:Prostaglandins; D016760:Proto-Oncogene Proteins c-fos; D012333:RNA, Messenger; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase