CCK

**Source and stimulus:** CCK is secreted by I cells in the duodenum and jejunum. The main stimuli are fatty acids (long-chain) and monoglycerides, and amino acids/small peptides (especially phenylalanine, tryptophan, methionine). Intraluminal CCK-releasing peptides also contribute.

**Actions (mnemonic: "CCK = Contract the Cholecyst, Kick out enzymes"):** - Gallbladder: contraction (via CCK-A receptors, Gq/PLC/IP3/Ca2+). - Sphincter of Oddi: relaxation, so bile and pancreatic juice enter the duodenum. - Pancreatic acinar cells: increases secretion of digestive enzymes (lipase, amylase, proteases). Its effect on ductal bicarbonate secretion is minor and potentiates secretin. - Stomach: decreases gastric emptying (the "enterogastric reflex" brake, which allows time for fat digestion) and inhibits acid secretion indirectly. - Satiety: acts on vagal afferents and the CNS to reduce food intake. - Trophic: promotes growth of the exocrine pancreas and gallbladder.

**Receptors:** CCK-A (alimentary) is found in the gallbladder, pancreas, and vagal afferents. CCK-B is identical to the gastrin receptor, found in the CNS and on parietal and ECL cells. Both are Gq-coupled.

**Comparison with other GI hormones:** - Gastrin (G cells): increases H+ secretion. It shares the same C-terminal pentapeptide as CCK, so there is some overlap in activity. - Secretin (S cells): increases pancreatic and biliary HCO3- secretion, and decreases gastric acid. - GIP (K cells): increases insulin release (the incretin effect) and decreases gastric acid. - Motilin: stimulates the migrating motor complex.

**Clinical correlations:** - Cholelithiasis/biliary colic: pain after fatty meals results from CCK-induced gallbladder contraction against an obstructing stone. - HIDA scan with CCK: CCK is given to stimulate gallbladder contraction. A gallbladder ejection fraction under about 35-40% suggests biliary dyskinesia or chronic acalculous cholecystitis. - Celiac disease: damage to duodenal mucosa reduces CCK release, leading to impaired gallbladder contraction and pancreatic secretion, which contributes to malabsorption. - Pancreatic insufficiency or fat malabsorption: raises CCK because of loss of negative feedback (pancreatic proteases degrade CCK-releasing peptide). - Total parenteral nutrition (no enteral stimulation): causes gallbladder stasis and sludge or stones, which can be mitigated by CCK or enteral feeding. - Octreotide: inhibits CCK release and gallbladder contraction, which predisposes to gallstones. - Gastric bypass or rapid weight loss: associated with gallstone formation, partly through reduced gallbladder motility. - CCK-B/gastrin receptor: CCK-B antagonists have been studied for anxiety (CCK-4 can induce panic attacks). - Proglumide is a CCK antagonist (non-USMLE high-yield).

**Regulation:** CCK release is inhibited by pancreatic proteases and bile in the duodenum (negative feedback). Somatostatin also inhibits it.

**High-yield one-liner:** Fat and protein in the duodenum release CCK from I cells. CCK contracts the gallbladder, relaxes the sphincter of Oddi, increases pancreatic enzyme secretion, and slows gastric emptying.