CCK, Satiety, and Associated Disorders

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CCK, Satiety, and Associated Disorders

• Ron Schneider

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What is CCK?

• CCK Cholecystikinin
• Peptide hormone
• Causes the Gallbladder (cholecyst) to contract
  releasing bile
• In response to presence of nutrients
• Pylorus to constrict and inhibits gastric
  contractions

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Nomenclature

• The term "cholecystokinin" originates from the
  Latin word chole for "bile and cysto for "sac",
  and kinin for "move".

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History of CCK

• 1856 Claude Bernard noted that Hydrochloric
  acid stimulated bile
• 1903 Wertheimer
• 1928 Ivy and Oldberg - small intestine hormone
  
• 1943 Harper and Raper - Pancreozymin (PZ)

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History of CCK

• 1968 Mutt identified CCK-33 as having maximal
  cholecystokinetic and panreozymic activity
• Mutt and Jorpes discovered Pancreozymin (PZ) CCK

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Distribution of CCK

• Small intestine endocrine l-cells
• CCK is synthesized in the brain as well

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CCK receptors

• 2 CCK subtype receptors have been discovered
• Alimentary CCK-A receptor
• CCK-B Receptor

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Structure of CCK
http//cellsignaling.lanl.gov/structure/kinase/tk/
cck4/cck4.2.jpg
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Digestive system
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Effects of CCK
Konturek et al, 2004
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Animal studies

• Animal studies have further illustrated the
  importance of CCK and its binding sites

Moran and Kinzig, 2004
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OLETF A CCK knockout Rodent

• Otsuka Long Evans Tokushima Fatty rats (OLETF)
• Insensitive to the feeding inhibitory actions of
  peripherally injected CCK-A
• Meal size Differs

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Gastrectomized Humans

• No difference in desire before or after meals as
  compared to controls
• Ate same amount of food
• But no increase in satiety

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Clinical aspects of CCK

• CCK is not only a gut peptide utilized in
  satiation, it can be useful in treating several
  disorders/illnesses such as eating disorders,
  enzymatic diseases as well as ways to better our
  general health

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Diagnostic uses

• CCK and the Gall bladder
• Secretin-CCK test
• Acalulous biliary disease
• Cystic duct syndrome
• Celiac disease
• Pentagastrin test

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Therapeutic uses

• CCK and its role in paralytic ileus
• Though more controlled studies are needed to
  determine its efficacy

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Abnormal expression of CCK

• CCK Assays
• Little in known about CCK in a diseased state
• New and research indicated CCK as playing an
  important role in certain disorders

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DSM-IV Bulimia Nervosa

• A. Recurrent episodes of binge eating.
• B. Recurrent inappropriate compensatory behavior
  in order to prevent weight gain
• C. . The binge eating and inappropriate
  compensatory behaviors
• D. Self-evaluation
• E. The disturbance does not occur exclusively
  during episodes of Anorexia Nervosa

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CCK and Bulimia

• Very little research until the last 10 years
• CCK-8

Benfeld and Ballenger, 1993
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CCK and Bulimia
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DSM-IV Anorexia Nervosa

• 1) Refusal to maintain body weight
• 2) intense fear of gaining weight or becoming fat
  
• 3) disturbance in the way in one's body weight,
  size, or shape is experienced

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CCK and Anorexia

• Little in know about the role of CCK and anorexia
• Dysfunctional satiety

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Other disorders

• Huntington's Disease
• Parkinsons disease

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Anxiety and CCK

• Extensive studies on CCK and anxiety/panic
  attacks have been carried out in the past few
  years
• CCK4 and Pentagastrin
• CI-988
• CCK-B antagonists

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CCK, Panic and Pentagastrin

• Pentagastrin is a potent CCK agonist and can
  cause panic attacks even in those who do not
  suffer from them

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Pentagastrin
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Final note on Schizophrenia

• CCK may play a role in schizophrenia
• CCK levels in CSF
• Deficits in CCK-related neurons in the limbic
  system associated with schizophrenia

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Conclusion

• CCK is involved with many systems in the body
• Satiety
• Anxiety
• Panic
• Pathology of CCK
• diagnostics