| Primary Identifier | IPR000596 | Type | Family |
| Short Name | Cholcy_rcpt_A |
| description | G protein-coupled receptors (GPCRs) constitute a vast protein family that encompasses a wide range of functions, including various autocrine, paracrine and endocrine processes. They show considerable diversity at the sequence level, on the basis of which they can be separated into distinct groups []. The term clan can be used to describe the GPCRs, as they embrace a group of families for which there are indications of evolutionary relationship, but between which there is no statistically significant similarity in sequence []. The currently known clan members include rhodopsin-like GPCRs (Class A, GPCRA), secretin-like GPCRs (Class B, GPCRB), metabotropic glutamate receptor family (Class C, GPCRC), fungal mating pheromone receptors (Class D, GPCRD), cAMP receptors (Class E, GPCRE) and frizzled/smoothened (Class F, GPCRF) [, , , , ]. GPCRs are major drug targets, and are consequently the subject of considerable research interest. It has been reported that the repertoire of GPCRs for endogenous ligands consists of approximately 400 receptors in humans and mice []. Most GPCRs are identified on the basis of their DNA sequences, rather than the ligand they bind, those that are unmatched to known natural ligands are designated by as orphan GPCRs, or unclassified GPCRs [].The rhodopsin-like GPCRs (GPCRA) represent a widespread protein family that includes hormone, neurotransmitter and light receptors, all of which transduce extracellular signals through interaction with guanine nucleotide-binding (G) proteins. Although their activating ligands vary widely in structure and character, the amino acid sequences of the receptors are very similar and are believed to adopt a common structural framework comprising 7 transmembrane (TM) helices [, , ].Cholecystokinins (CCKs) and gastrins are naturally-occurring peptides that share a common C-terminal sequence, GWMDF; full biological activity resides in this region. In the periphery, the principal physiological actions of CCK include gall bladder contraction, pancreatic enzyme secretion and regulation of secretion/absorption in the gastrointestinal tract. In the CNS, CCK induces analgesia, satiety and a decrease in exploratory behaviour. In mesolimbic andmesocortical neurons, CCK coexists with dopamine. It is found throughout the digestive tract, with high concentrations in the duodenum and jejunum. It is also found in peripheral nerves to other smooth muscles and to secretory glands, and is one of the most abundant peptides in the brain. The highest levels of the CCKA receptor are found in peripheral tissues, notably the pancreas, stomach, intestine and gall bladder. It has only a limited distribution in the brain. The receptor has been implicated in the pathogenesis of schizophrenia, Parkinson's disease, drug addiction and feeding disorders. |
