Cholecystokinin receptors (nomenclature as agreed by the NC-IUPHAR Subcommittee on CCK receptors [20]) are activated by the endogenous peptides cholecystokinin-8 (CCK-8 (CCK, P06307)), CCK-33 (CCK, P06307), CCK-58 (CCK, P06307) and gastrin (gastrin-17 (GAST, P01350)). There are only two distinct subtypes of CCK receptors, CCK₁ and CCK₂ receptors [15,29], with some alternatively spliced forms most often identified in neoplastic cells. The CCK receptor subtypes are distinguished by their peptide selectivity, with the CCK₁ receptor requiring the carboxyl-terminal heptapeptide-amide that includes a sulfated tyrosine for high affinity and potency, while the CCK₂ receptor requires only the carboxyl-terminal tetrapeptide shared by each CCK and gastrin peptides. These receptors have characteristic and distinct distributions, with both present in both the central nervous system and peripheral tissues.

While a cancer-specific CCK receptor has been postulated to exist, which also might be responsive to incompletely processed forms of CCK (Gly-extended forms), this has never been isolated. An alternatively spliced form of the CCK₂ receptor in which intron 4 is retained, adding 69 amino acids to the intracellular loop 3 (ICL3) region, has been described to be present particularly in certain neoplasms where mRNA mis-splicing has been commonly observed [24], but it is not clear that this receptor splice form plays a special role in carcinogenesis. Another alternative splicing event for the CCK₂ receptor was reported [25], with alternative donor sites in exon 4 resulting in long (452 amino acids) and short (447 amino acids) forms of the receptor differing by five residues in ICL3, however, no clear functional differences have been observed.

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Subcommittee members: Laurence J. Miller (Chairperson) Mayo Clinic 13400 East Shea Boulevard Scottsdale AZ 85259 USA Margery Beinfeld Dept. of Pharmacology & Experimental Therapeutics Tufts University School of Medicine 136 Harrison Avenue Boston, MA 02111 Roger A. Liddle DUMC 3913 Durham, NC 27710 USA Jens Rehfeld Department of Clinical Biochemistry Rigshospitalet University of Copenhagen Denmark