L-arginine-NO-cGMP signalling pathway in pancreatitis

Abstract

The role of nitric oxide (NO) in the human pancreas and in pancreatitis still remains controversial. Furthermore, conflicting conclusions have been reached by different laboratories about the localization of the NO-generating enzyme (NO synthase, NOS) in the pancreas. Here, we investigated the co-expression of NOS with enzymes involved in regulation of NO signalling in the normal human pancreas and in pancreatitis. We found that the whole NO signalling machinery was up-regulated in pancreatitis, especially within the exocrine compartment. Furthermore, the exocrine parenchymal cells revealed higher levels of oxidative stress markers, nitrotyrosine and 8-hydroxyguanosine, in pancreatitis, which reflects the exceptional susceptibility of the exocrine parenchyma to oxidative stress. This study provides a direct link between oxidative stress and the enzymatic control of the NO bioavailability at the cellular level and endows with further insight into fundamental mechanisms underlying pancreatic disorders associated with disruptions in the L-arginine-NO-cGMP signalling enzyme cascade.

Sodium Butyrate Ameliorates l‐Arginine‐Induced Pancreatitis and Associated Fibrosis in Wistar Rat: Role of Inflammation and Nitrosative Stress

“…Furthermore, SB treatment increased beta‐cell proliferation and improved glucose homeostasis . l ‐Arg treatment significantly increases the oxidative and nitrosative stress, which leads to inflammatory response and finally causes the acinar cell damage . SB treatment decreased the oxidative and nitrosative stress, histological alterations such as acinar cell atrophy, vacuolization, inflammatory cells infiltration, and fibrosis.…”

Nitric oxide signals are interlinked with calcium signals in normal pancreatic stellate cells upon oxidative stress and inflammation

“…The authors of the study, however, did not refer directly to PSCs, although they report the presence of ‘cells of the morphology of ductal cells’ in chronic pancreatitis (CP) tissue specimens [55]. These cells could well have been PSCs, which are known to induce fibrosis in CP [2,56].…”

cCMP and cUMP occur in vivo

“…The high cGMP levels in bladder fit to the role of this cNMP in smooth muscle relaxation [30]. The identification of relatively high cGMP levels in pancreas was unexpected, but upregulation of cGMP signaling in pancreatitis has been reported [31]. Equally surprising was the finding that in lung, cGMP levels were rather low although cGMP plays an important role in lung function [32].…”