Secretin, a member of the secretin-glucagon peptide hormone family, is a 27 amino acid peptide that was originally isolated from the duodenum. In the duodenum, secretin is released to stimulate the release of digestive juices in the pancreas (Bayliss et al, 1902). The receptor for secretin is a class 2 (or class B) G protein coupled receptor that signals through Gs to stimulate cAMP production (Dong et al, 2002). Along with its traditional role in the pancreas, studies in secretin-deficient mice have shown miscommunication between the CA3 Schaffer collateral and CA1 pyramidal neurons, causing a deficiency in synaptic transmission (Nishijima et al, 2006). This miscommunication of CA1 dendrites is found in Autism, Rett Syndrome, and most forms of mental retardation, suggesting secretin could be a potential target for treatment of these disorders. The cloned human Secretin Receptor-expressing cell line is made in the Chem-1 host, which supports high levels of recombinant Secretin Receptor expression on the cell surface and contains high levels of the promiscuous G protein Gα15 to couple the receptor to the calcium signaling pathway. Thus, the cell line is an ideal tool for screening for antagonists of interactions between the Secretin Receptor and its ligands.