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Cholecystokinin (CCK)
A peptide hormone produced in the duodenum that stimulates gallbladder contraction, pancreatic enzyme secretion, and acts as a satiety signal, with additional roles as a neurotransmitter in the brain.
Overview
Cholecystokinin (CCK) is a peptide hormone discovered in 1928 by Andrew Ivy and Eric Oldberg, who identified a substance in intestinal extracts that could stimulate gallbladder contraction (hence the name: "cholecysto" = gallbladder, "kinin" = to move). It exists in multiple molecular forms (CCK-8, CCK-22, CCK-33, CCK-58) produced by post-translational processing of a single precursor protein, with CCK-8 being the most potent form.
CCK is primarily synthesized by I-cells in the duodenal and jejunal mucosa in response to the presence of fats and proteins in the small intestinal lumen. It acts through two G-protein coupled receptor subtypes: CCK-A (now CCK-1), primarily found in the gastrointestinal tract, and CCK-B (now CCK-2), predominantly found in the brain. Through CCK-1 receptors, CCK stimulates gallbladder contraction, pancreatic enzyme secretion, and relaxation of the sphincter of Oddi, facilitating the digestion and absorption of dietary fats.
One of CCK's most important physiological roles is as a satiety signal. Released postprandially, CCK acts on vagal afferent neurons to transmit satiety signals to the brain, leading to meal termination. This anorexigenic effect has made CCK receptors targets for anti-obesity drug development, though short-term satiety effects have not consistently translated to sustained weight loss in clinical trials.
In the central nervous system, CCK functions as a neurotransmitter with diverse roles. It is one of the most abundant neuropeptides in the brain, involved in anxiety and panic responses (particularly through CCK-2 receptors), pain modulation, memory, and the regulation of dopamine signaling. CCK-4, a synthetic tetrapeptide fragment, reliably induces panic attacks in human subjects and has been used as a research tool for studying panic disorder. The interaction between CCK and dopamine systems has implications for understanding schizophrenia and addiction.