Bile‐Pancreatic Juice Exclusion Induces Expression of RGS6 in Rat Exocrine Pancreas

RGS ( R egulator of G protein signaling) proteins are a family of proteins that negatively regulate heterotrimeric G protein signaling. This activity is believed to result largely from their GAP activity towards Gα subunits, terminating Gα and Gβγ signaling, and by actions of some RGS proteins on receptors or G protein effectors. Dialysis of RGS proteins into pancreatic acinar cells was shown previously to inhibit signaling by G protein coupled CCK‐A and cholinergic receptors. Bile‐pancreatic juice (BPJ) exclusion from the duodenum produces “hyperstimulation” of the pancreas by neural (cholinergic) and humoral (CCK) mechanisms. Here, we identified RGS6 in the pancreas and determined whether BPJ exclusion induces its expression. Bile pancreatic ducts in rats were cannulated for external diversion of BPJ or subjected to sham duct dissection alone, and pancreata were harvested one and three hours later. Immunoblots of RGS6 in pancreatic homogenates showed that BPJ exclusion for one and three hours produced a dramatic increase in RGS6 expression. Likewise, BPJ exclusion for one hour induced expression of RGS6 mRNA, which was not detected by PCR in sham controls. Immunohistochemistry of pancreatic sections showed that RGS6 was induced by BPJ exclusion and was localized in the cytosol of pancreatic acinar cells. These results provide new evidence for regulation of RGS6 expression in pancreatic acinar cells in vivo during hyperstimulation of the pancreas by BPJ exclusion, raising the intriguing possibility that RGS6 may inhibit pancreatic acinar cell responses to hyperstimulation and ameliorate acute pancreatitis. (NIH GM067881 and DK062805)