Cav 1.2 and Cav 2.2 expression is regulated by different endogenous ghrelin levels in pancreatic acinar cells during acute pancreatitis.

Abstract

Ghrelin influences pancreatic endocrine and exocrine functions, regulates intracellular calcium [Ca2+]i levels, and has an anti-inflammatory role in acute pancreatitis. This study investigated the role of endogenous ghrelin in the expression of Cav1.2 (L-type of Ca2+ channel) and Cav2.2 (N-type of Ca2+ channel) in acute pancreatitis. For this purpose, acute edematous pancreatitis (AEP) and acute necrotizing pancreatitis (ANP) rat models were established. Cav1.2 and Cav2.2 expression was assessed by immunohistochemistry in the pancreatic tissues of rats; ghrelin, interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) serum levels were detected using ELISA. Next, in AR42J cells with either knock-out or overexpression of ghrelin, Cav1.2 and Cav2.2 expression was examined using western blot analysis, and intracellular calcium [Ca2+]i was detected with confocal microscopy. In this study, the ghrelin serum level was highest in the ANP group and was higher in the AEP group than the normal group. Expression of Cav1.2 and Cav2.2 in the ANP and AEP groups was higher than in the respective control groups. The serum IL-1β and TNF-α levels were significantly higher in the ANP group compared to the other groups. Cav1.2 and Cav2.2 expression and [Ca2+]i decreased in ghrelin knockdown AR42J cells but increased in ghrelin overexpressing cells. In conclusion, Cav1.2 and Cav2.2 expression increased in ANP. The [Ca2+]i level, which is mediated by Cav1.2 and Cav2.2 expression, is directly regulated by ghrelin in pancreatic acinar cells, and serum ghrelin levels may be involved in the severity of acute pancreatitis.