Chemical Identity

CCK-58 (Full-Length)

Property	Value
Name	Cholecystokinin-58
Gene	CCK (chromosome 3q13.3)
Sequence	DYMGWMDFGRRQEEPVSKPP西湖EDGAPRKGAILIKVSSWFNQRAKNH (58 aa)
Abbreviation	CCK-58
Length	58 amino acids
C-terminal	Amidated sulfated tyrosine (Tyr-SO₃H)

CCK Isoforms

Isoform	Length	Source	Primary Function
CCK-58	58 aa	GI tract (dominant)	Satiety, gallbladder
CCK-33	33 aa	GI tract	Pancreatic secretion
CCK-22	22 aa	Brain	Neurotransmission
CCK-8	8 aa	Brain, GI	Satiety, neurotransmission

CCK-8 (Most Studied)

Property	Value
Sequence	Asp-Tyr-Met-Gly-Trp-Met-Asp-Phe-NH₂
Abbreviation	DYMGWMDF-NH₂
Sulfation	Tyr-sulfated (CCK-8S) or non-sulfated (CCK-8NS)
MW	1094.3 Da (sulfated)

Receptors

Receptor	Gene	Distribution	Affinity
CCK-A (CCK1R)	CCKAR	Gallbladder, pancreas, stomach, vagus nerve	Sulfated CCK-8 (Kd ~1 nM)
CCK-B (CCK2R)	CCKBR	Brain, stomach	CCK-8, gastrin (Kd ~5 nM)

Signaling

CCK → CCK-A (GI) or CCK-B (Brain)
    → Gαq → PLC → IP₃ + DAG
    → ↑ Ca²⁺ → Smooth muscle contraction
    → ↑ cAMP → Enzyme secretion

Physiological Functions

Gallbladder Contraction

• CCK-8S is the primary stimulus for gallbladder contraction
• Released by I-cells in response to dietary fat and amino acids
• Activates CCK-A receptors on gallbladder smooth muscle
• Results in bile release into duodenum for fat digestion

Pancreatic Secretion

• Stimulates pancreatic acinar cells via CCK-A receptors
• Increases enzyme (amylase, lipase, protease) secretion
• Synergistic with secretin for bicarbonate secretion

Satiety

• CCK-8 released from GI tract during meals
• Activates vagal afferents (CCK-A receptors)
• Signals to hypothalamus → appetite suppression
• Short-term: Reduces meal size
• Long-term: Weight regulation

Other Functions

• Gastric acid: Modulates gastric acid secretion
• GI motility: Delays gastric emptying
• Brain: Neurotransmitter (CCK-B receptors)
• Pain: Modulates visceral pain perception

Clinical Significance

Cholecystokinin Receptor Antagonists

Drug	Target	Indication	Status
Devazepide	CCK-A	GI disorders	Research
Proglumide	CCK-B	GI disorders	Approved (limited)
Loxiglumide	CCK-A	Pancreatitis	Research
Lorglumide	CCK-A	Pancreatitis	Research

Diagnostic Applications

• CCK-stimulated cholescystigraphy: CCK injection → gallbladder contraction → diagnostic imaging
• CCK-HIDA scan: Functional gallbladder assessment
• Serum CCK levels: Biomarker for GI disorders

Disease Associations

• Gallstones: CCK hypersecretion may contribute
• Pancreatitis: CCK receptor dysfunction
• Obesity: CCK signaling defects
• Anxiety: CCK-B receptor polymorphisms

Manufacturing

CCK-8S Synthesis

1. SPPS (Fmoc): Solid-phase synthesis
2. Tyr sulfation: Post-synthetic or on-resin
3. C-terminal amidation: Required for activity
4. Purification: RP-HPLC
5. Characterization: MS, NMR

References

1. Liddle RA. “Regulation of CCK secretion.” Annual Review of Physiology 57:339-360, 1995. doi:10.1146/annurev.ph.57.030196.002313
2. Moran TH, et al. “CCK and the regulation of feeding.” Peptides 25:721-730, 2004.
3. Rehfeld JF, et al. “CCK isoforms: structure, function, and physiology.” Gastroenterology 128:1552-1567, 2005.
4. Wank SA. “Gastrointestinal hormones: CCK receptors.” American Journal of Physiology 269:G715-G730, 1995.
5. Smith GP, et al. “CCK and the control of food intake.” American Journal of Physiology 257:G1135-G1140, 1989.