Regulation of cholecystokinin-mediated amylase secretion by leptin in rat pancreatic acinar tumor cell line AR42J

Expression of the long form of the leptin receptor,the isoform that is cons idered to have full signaling capability, has been reported in the central nervous system and several peripheral cell types. However, only a few cell lines have been shown to express the long form of the receptor. AR42J, a ce ll line derived from azaserine-treated rat pancreas, is a common model for pancreatic acinar cell secretion. In this study, the presence of leptin-rec eptor variants and leptin action was evaluated in this cell line. Messenger RNAs for both the long and a short form of the leptin receptor were detect ed by reverse transcription-polymerase chain reaction (RT-PCR) in AR42J cel ls, and authenticity of the receptor was confirmed by DNA sequencing. Compe titive binding studies demonstrated that binding of radiolabeled leptin was specific and did not cross- react with cholecystokinin (CCK). Biologic eff ects of leptin on amylase release and intracellular calcium mobilization we re further assessed in the presence and the absence of CCK, a known pancrea tic secretogogue. Although leptin alone (less than or equal to 200 ng/ml) d id not affect basal amylase release, it inhibited amylase release stimulate d by 1 nM CCK by 48%. Leptin alone had no significant effect on calcium mob ilization. However, pretreat ment of leptin (10 and 100 ng/ml) enhanced cal cium responses stimulated by CCK. These data demonstrate that the rat pancr eatic tumor cell line AR42J expresses a functional form of the leptin recep tor that modulates the action of CCK in calcium mobilization and amylase re lease.