Molecular Cloning, Functional Expression and Chromosomal Localization of the Human Cholecystokinin Type A Receptor

The cholecystokinin (CCK) family of peptides and receptors are present throughout the brain and gastrointestinal tract and can be pharmacologically subdivided into two subtypes: CCKA and CCKB. Little is known about the localization, pharmacology and function of CCKA receptors (CCKAR) in humans. We used the rat CCKAR cDNA to isolate the human CCK receptor cDNA homologue from human gallbladder which encodes a unique 428 amino acid protein having >90% homology to the rat and guinea pig CCKAR. Expression of the recombinant CCKAR in COS-7 cells displayed a pharmacological profile characteristic of a CCKAR subtype and mediated agonist stimulated increase in total inositol phosphates. Northern hybridization identified a transcript measuring 6 Kb. The human CCKAR gene maps to chromosome 4. These results describe for the first time the molecular cloning, expression and chromosomal localization of the human CCKA receptor.