Cholecystokinin (CCK)
Overview
Cholecystokinin is an endogenous peptide hormone existing in multiple forms, most commonly as CCK-8 and CCK-33, secreted by I-cells in the duodenum and jejunum. It binds to CCK-1 and CCK-2 receptors to stimulate gallbladder contraction, pancreatic enzyme secretion, and satiety signaling. Therapeutic interest centers on diagnostic imaging applications and potential treatments for obesity and functional gastrointestinal disorders. The peptide also plays neuromodulatory roles in the central nervous system.
Key Research Findings
Sincalide, a synthetic CCK-8 analog, is FDA approved for diagnostic use to stimulate gallbladder contraction during cholescintigraphy and to stimulate pancreatic secretion for sample collection. Clinical trials exploring CCK analogs for obesity have shown limited efficacy due to rapid desensitization and gastrointestinal side effects. Research continues into selective CCK receptor modulation for metabolic and gastrointestinal applications.
Intravenous
FDA Approved
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Octreotide (Sandostatin)
FDA ApprovedA synthetic octapeptide analog of somatostatin with a substantially longer half-life (90 minutes IV, 6 hours subcutaneous vs. 2 minutes for native somatostatin). Octreotide binds somatostatin receptors (primarily SSTR2 and SSTR5) to inhibit the secretion of GH, glucagon, insulin, gastrin, secretin, VIP, and other GI hormones. It reduces splanchnic blood flow, GI motility, and exocrine pancreatic secretion.
Lanreotide (Somatuline Depot)
FDA ApprovedA synthetic octapeptide analog of somatostatin with high affinity for SSTR2 and moderate affinity for SSTR5 receptors. Lanreotide is formulated as a supersaturated solution that forms a drug depot at the injection site, providing sustained release over 4 weeks. It inhibits GH secretion, GI hormone release, and has direct antiproliferative effects on neuroendocrine tumor cells through cell cycle arrest and apoptosis induction.
Pasireotide (Signifor)
FDA ApprovedA multireceptor-targeted somatostatin analog with high binding affinity for SSTR1, SSTR2, SSTR3, and SSTR5, particularly notable for its 40-fold greater affinity for SSTR5 compared to octreotide. This receptor profile makes pasireotide uniquely effective in Cushing's disease, where corticotroph adenomas predominantly express SSTR5. Pasireotide suppresses ACTH secretion from pituitary corticotroph tumors, reducing cortisol production.
Plecanatide (Trulance)
FDA ApprovedA synthetic 16-amino acid peptide structurally related to uroguanylin, an endogenous intestinal peptide that regulates fluid and electrolyte homeostasis in the GI tract. Plecanatide activates guanylate cyclase-C (GC-C) receptors on intestinal epithelial cells in a pH-dependent manner, preferentially in the proximal small intestine where pH is slightly acidic. GC-C activation increases intracellular and extracellular cGMP, stimulating chloride and bicarbonate secretion while reducing visceral pain signaling.