Dm. Harris et al., Regulation of cholecystokinin-mediated amylase secretion by leptin in rat pancreatic acinar tumor cell line AR42J, PANCREAS, 19(3), 1999, pp. 224-230
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.