Human pancreatic acinar cells lack functional responses to cholecystokinin and gastrin

Background & Aims: Pancreatic acinar cells from various species express cholecystokinin (CCK) A, CCK-B, or a combination of these CCK receptor subtypes. The presence and functional roles of CCK receptors on human acinar cells remain unclear. Methods: Acini isolated from human pancreas were treated with CCK receptor agonists, CCK-8 and gastrin, and an agonist for m3 muscarinic acetylcholine receptors (m3 AchR), carbachol. Functional parameters measured included intracellular [Ca2+], amylase secretion, and ERK phosphorylation. Binding studies were performed using I-125-CCK-8. Expression of messenger RNAs (mRNAs) was determined using real-time quantitative reverse-transcription polymerase chain reaction (RT-PCR) and localized by in situ hybridization. Results: Human acini did not respond to CCK agonists. In contrast, they responded to carbachol with robust increases in each of the functional parameters. Moreover, the cells responded to CCK agonists after adenoviral-mediated gene transfer of CCK-A or CCK-B receptors. A low level of specific and a high level of nonspecific binding of I-125-CCK-8 were observed. Quantitative RT-PCR indicated that the message levels for CCK-A receptors were similar to 30-fold lower than those of CCK-B receptors, which were similar to 10-fold lower than those of m3 Ach receptors. In situ hybridization indicated the presence of m3 Ach receptor and insulin mRNA but not CCK-A or CCK-B receptor mRNAs in adult human pancreas. Conclusions: These data indicate that human pancreatic acinar cells do not respond to CCK receptor agonists in terms of expected functional parameters and show that this is due to an insufficient level of receptor expression.