Gastrin and cholecystokinin (CCK) are structurally and functionally related peptide hormones that function as hormonal regulators of various digestive processes and feeding behaviours. They are known to induce gastric secretion, stimulate pancreatic secretion, increase blood circulation and water secretion in the stomach and intestine, and stimulate smooth muscle contraction. Originally found in the gut, these hormones have since been shown to be present in various parts of the nervous system. Like many other active peptides they are synthesized as larger protein precursors that are enzymatically converted to their mature forms. They are found in several molecular forms due to tissue-specific post-translational processing. A number of other peptides are known to belong to the same family: Caerulein, an amphibian skin peptide, with a biological activity similar to that of CCK or gastrin. There are different types of caerulein []in which a single or up to four copies of the peptide are present. Leukosulfakinin I and II (LSK) [, ]are peptides, isolated from cockroach, that change the frequency and amplitude of contractions of the hindgut. Drosulfakinins I and II []are putative CCK-homologues from Drosophila. Those two peptides are part of a precursor sequence that was isolated using a probe based on the sequence of CCK and LSK. A chicken antrum peptide []which is a potent stimulus of avian gastric acid but not of pancreatic secretion. Cionin [], a neuropeptide from the protochordate Ciona intestinalis (Transparent sea squirt). The biological activity of gastrin and CCK is associated with the last five C-terminal residues. One or two positions downstream, there is a conserved sulphated tyrosine residue.
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.
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 thatshare a common C-terminal sequence, GWMDF; full biological activity residesin this region. In the periphery, the principal physiological actions ofCCK include gall bladder contraction, pancreatic enzyme secretion andregulation of secretion/absorption in the gastrointestinal tract. In theCNS, CCK induces analgesia, satiety and a decrease in exploratory behaviour.In mesolimbic and mesocortical neurons, CCK coexists with dopamine. Itis found throughout the digestive tract, with high concentrations in theduodenum and jejunum. It is also found in peripheral nerves to other smoothmuscles and to secretory glands, and is one of the most abundant peptides inthe brain. The principal physiological role of gastrin is to stimulateacid secretion in the stomach; it also has trophic effects on gastric mucosa. It is found predominantly in the stomach and intestine, but also invagal nerves.
Gastrin and cholecystokinin (CCK) are structurally and functionally related peptide hormones that function as hormonal regulators of various digestive processes and feeding behaviours. They are known to induce gastric secretion, stimulate pancreatic secretion, increase blood circulation and water secretion in the stomach and intestine, and stimulate smooth muscle contraction. Originally found in the gut, these hormones have since been shown to be present in various parts of the nervous system. Like many other active peptides they are synthesized as larger protein precursors that are enzymatically converted to their mature forms. They are found in several molecular forms due to tissue-specific post-translational processing. The biological activity of gastrin and CCK is associated with the last five C-terminal residues. One or two positions downstream, there is a conserved sulphated tyrosine residue. The amphibian caerulein skin peptide, the cockroach leukosulphakinin I and II (LSK) peptides, Drosophila melanogaster putative CCK-homologues Drosulphakinins I and II, cionin, a chicken gastrin/cholecystokinin-like peptide and cionin, a neuropeptide from the protochordate Ciona intestinalis belong to the same family.This entry refers to cholecystokinin and cholecystokinin-like proteins including cholecystoxin and preprocaerulein.
Gastrin and cholecystokinin (CCK) are structurally and functionally related peptide hormones that function as hormonal regulators of various digestive processes and feeding behaviors. They are known to induce gastric secretion, stimulate pancreatic secretion, increase blood circulation and water secretion in the stomach and intestine, and stimulate smooth muscle contraction. Originally found in the gut, these hormones have since been shown to be present in various parts of the nervous system. Like many other active peptides they are synthesized as larger protein precursors that are enzymatically converted to their mature forms. They are found in several molecular forms due to tissue-specific post-translational processing. The biological activity of gastrin and CCK is associated with the last five C-terminal residues. One or two positions downstream, there is a conserved sulphated tyrosine residue. The amphibian caerulein skin peptide, the cockroach leukosulphakinin I and II (LSK) peptides, Drosophila melanogaster (Fruit fly) putative CCK-homologues Drosulphakinins I and II, cionin, a Gallus gallus (Chicken) gastrin/cholecystokinin-like peptide and cionin, a neuropeptide from the protochordate Ciona intestinalis belong to the same family.
