Human pancreatic acinar cells lack functional responses to cholecystokininand gastrin

Background & Aims: Pancreatic acinar cells from various species express cho lecystokinin (CCK) A, CCK-B, or a combination of these CCK receptor subtype s. The presence and functional roles of CCK receptors on human acinar cells remain unclear. Methods: Acini isolated from human pancreas were treated w ith CCK receptor agonists, CCK-8 and gastrin, and an agonist for m3 muscari nic acetylcholine receptors (m3 AchR), carbachol. Functional parameters mea sured included intracellular [Ca2+], amylase secretion, and ERK phosphoryla tion. Binding studies were performed using I-125-CCK-8. Expression of messe nger RNAs (mRNAs) was determined using real-time quantitative reverse-trans cription polymerase chain reaction (RT-PCR) and localized by in situ hybrid ization. Results: Human acini did not respond to CCK agonists. In contrast, they responded to carbachol with robust increases in each of the functiona l parameters. Moreover, the cells responded to CCK agonists after adenovira l-mediated gene transfer of CCK-A or CCK-B receptors. A low level of specif ic and a high level of nonspecific binding of I-125-CCK-8 were observed. Qu antitative RT-PCR indicated that the message levels for CCK-A receptors wer e similar to 30-fold lower than those of CCK-B receptors, which were simila r to 10-fold lower than those of m3 Ach receptors. In situ hybridization in dicated the presence of m3 Ach receptor and insulin mRNA but not CCK-A or C CK-B receptor mRNAs in adult human pancreas. Conclusions: These data indica te that human pancreatic acinar cells do not respond to CCK receptor agonis ts in terms of expected functional parameters and show that this is due to an insufficient level of receptor expression.