Question:

In the pancreatic exocrine gland, nitric oxide (NO) exerts functional roles in the machinery of exocrine secretion because (i) it induces secretion by mobilizing Ca²⁺ from IP₃-sensitive stores via a cGMP pathway ; (ii) aberrant Ca²⁺ signals and leak of digestive enzymes have been described upon a decreased synthesis by NO synthase in occasion of an acute pancreatitis; and (iii) synthesis of cGMP appears to exert a protective effect in this desease. Considering that the effects of NO are intermediated largely by soluble guanylyl cyclase (sGC), we tested the hypothesis that cGMP interferes with both the cytoplasmic Ca²⁺ signals and the enzyme secretion in pancreatic acinar cells stimulated with either cholecystokinin (CCK) or a bile acid.

Methods:

To assess the role of cGMP in either the Ca²⁺ signaling or trypsin activation and secretion, a pharmacological approach was adopted by using the sGC stimulator 1-nitro-2-phenylethane (NPE) in freshly isolated mouse pancreatic acinar cells marked with a Ca²⁺ or a trypsin fluorescent subtrate, respectively. All the data were analysed by confocal microscopy.

Results:

The NPE partly reverts, in a ODQ-preventable manner, the Ca²⁺ responses induced by CCK offerred at pathological levels, but did not modify the signal induced by taurocholate. Alone, NPE induces the intracellular activation and the secretion of the trypsin in a bell shape manner, but protects partially the cells from the necrosis induced by taurocholate.

Conclusion:

The NO/cGMP pathway may modulate the Ca²⁺ signaling and enzyme secretion in mouse pancreatic acinar cells.