Discovery
CCK is released from I-cells in the small intestine. CCK
stimulates gall bladder contraction and pancreatic enzyme
secretion. In the central nervous system, CCK is implicated
in anxiogenesis, satiety, appetite, nociception, memory, and
learning. In 1928, CCK was first described as an inducer of gall
bladder contractions derived from the small intestines of
dogs and cats. Pig intestine extracts were known to
contain a substance called pancreozymin, which stimulated the secretion of pancreatic enzymes. In 1962, a
33-aa peptide isolated from pig intestines was reported
to activate both gall bladder contractions (CCK action)
and pancreatic enzyme secretion (pancreozymin action).
The sequence of porcine CCK/pancreozymin was
determined in 1968.
Structure
Human preproCCK consists of 115 aa residues. Bioactive peptides of varying lengths with different N-terminal
extensions (CCK-58, CCK-33, CCK-22, CCK-12, CCK-8,
and CCK-4) are produced by enzymatic processing.
CCK possesses a sulfated tyrosine at the seventh residue
from the C-terminus. The C-terminal phenylalanine residue is amidated. In vertebrates, the amino acid sequences of CCKs are
highly conserved, particularly in the C-terminal sequence
that retains biological activity .
Gene, mRNA, and precursor
The human preproCCK gene, CCK, location 3p22.1,
contains five exons. CCK mRNA is 1511 bases in length
and encodes a precursor of 115 aa residues. The CCK gene is expressed in the I-cells of the duodenum and small intestine. In rats, Cck is expressed in the
brain, heart, lung, kidney, and small intestine.
Synthesis and release
In intestinal I-cells, dietary lipids and proteins are
sensed by GPR40 and the calcium-sensing receptor,
respectively, resulting in the stimulation of CCK release.
Receptors
The CCK1 receptor (CCK1R) and CCK2 receptor
(CCK2R) are GPCRs that have seven transmembrane
domains. Human CCK1R consists of 428 aa residues.
CCK binds to CCK1R with 500 to 1000 times the affinity
and potency of gastrin and nonsulfated CCK. The sulfation of CCK is essential for receptor activation. The dissociation constants (Kd) of CCK-8 and nonsulfated CCK-8
with CCK1R are 1 and 500 nM, respectively.
Agonists and Antagonists
CCK, A-71623, GW-5823. Devazepide, Lintitript, Lorglumide, PD-140548,
T-0632.
Biological functions
CCK stimulates contraction of the gall bladder and
secretion of pancreatic enzymes via CCK1R. CCK affects
the vagal afferent neurons in paracrine and endocrine
manners via CCK1R and inhibits gastric emptying and
food intake. Insulin secretion is induced by CCK stimulation. In the central nervous system, CCK is implicated
in anxiogenesis, satiety, appetite, nociception, memory,
and learning.
Description
Cholecystokinin is the most widespread and abundant peptide in the brain, with only the mature cerebellum possibly devoid of representation. Interest in this peptide also stems from its potency, prominent colocalization with dopamine, nonsynaptic associations influencing neuronal excitability and cerebral blood flow, and putative links to several neuropsychiatric disorders (Rehfeld 1992a, 1992b).
Uses
Cholecystokinin is a peptide hormone. Cholecystokinin, as a hunger suppressant, inhibits food intake and stimulates the digestion of fat and protein. Cholecystokinin can be used for the research of gastrointestinal system[1][2][3].
General Description
Receptor interacting serine/threonine kinase 2 (RIPK2) or RICK is a serine/threonine kinase. It contains a kinase domain at the amino-terminal, an intermediate domain and a caspase activation and recruitment domain (CARD) at the carboxy-terminal. The gene encoding RIPK2 is localized on human chromosome 8q21.3.
Biochem/physiol Actions
Receptor interacting serine/threonine kinase 2 (RIPK2) or RICK is activated during innate immune responses and acts as a scaffold for downstream effectors. It functions in nuclear factor-κB (NFκB) activation pathways. The protein also has roles in toll-like receptor (TLR)-signaling pathways and in the production of inflammatory cytokines.
References
[1] G P Smith, et al. Abdominal vagotomy blocks the satiety effect of cholecystokinin in the rat. Science. 1981 Aug 28;213(4511):1036-7. DOI:
10.1126/science.7268408[2] R A Liddle, et al. Cholecystokinin cells. Annu Rev Physiol. 1997;59:221-42. DOI:
10.1146/annurev.physiol.59.1.221[3] Dockray, Graham J. Cholecystokinin. Curr Opin Endocrinol Diabetes Obes. 2012 Feb;19(1):8-12. DOI:
10.1097/MED.0b013e32834eb77d
