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    Caerulein and Analogs、雨蛙素及類似物
    • Caerulein and Analogs、雨蛙素及類似物

      Definition

      Caerulein is a decapeptide obtained from the skin of an Australian amphibian1.  It stimulates gastric, biliary and pancreatic secretion and is used as a diagnostic tool in pancreatic malfunctions1. 

      Discovery

      Caerulein was first isolated from the skin of the frog, Hyla caerulea based on the ability of its preparation to stimulate secretion of gastric and pancreatic juices from other experimental animals1,2.

      Classification

      Caerulein is very similar to cholecystokinin which belongs to gastrin-type family of hormones3. 

      Structural Characteristics

      Caerulein is a decapeptide with the sequence Pyr-Gln-Asp-Tyr(SO3H)-Thr-Gly-Trp-Met-Asp-Phe-NH23.  The tyrosine sulphate residue is critical for its biological activity4. Caerulein analogs have related structure to caerulein but their functional potencies vary.  Some of the analogs of caerulein include Caerulein 2.1, 3.1, 4.1 (all containing Met) and 2.2, 3.2 and 4.2 (all containing Phe)4. 

      Mode of action

      Caerulein exerts its functions by binding to two types of receptors, CCK1 and CCK2.  CCK1 receptor binding directly results in smooth muscle contraction4.  Caerulein binds to CCK2 receptors on pancreatic delta cells and triggers the secretion of pancreatic juice. Specifically, it stimulates the hydrolysis of phosphatidylinositol bisphosphate to form inositol trisphosphate and diacylglycerol5. The released inositol trisphosphate could function as a second messenger to mobilize Ca2+ from an intracellular store which in turn stimulates exocytosis5. 

      Functions

      Caerulein produces several behavioral effects in mammals such as inhibition of food and water intake, changes in mood, analgesia, sedation and antipsychotic effects6.  Caerulein also stimulates the secretion of pancreatic, bile and gastric juices1.   

      References 

      1. Anastasi A, Erspamer V & Endean R (1967). Isolation and structure of caerulein, an active decapeptide from the skin of Hyla caerulea. Experientia, 23, 699-700.

      2. Anastasi A, Erspamer V & Endean R (1968). Isolation and amino acid sequence of caerulein, the active decapeptide of the skin of Hyla caerulea. Arch. Biochem. Biophys., 125, 57-68.

      3. Caro GD, Endean R, Erspamer V and Roseghini M (1968). Occurrence of Caerulein in extracts of the skin of Hyla caerulia and other Australian hylids. Br. J. Pharmac. Chemother, 33, 48-58.

      4. Book: Handbook of Biologically active peptides by Abba J Kastin, Pg 285.

      5. Roberto B, Tullio P and Claes BW (1986). Caerulein and carbamoylcholine stimulate pancreatic amylase release at resting cytosolic free Ca2+. Biochem. J., 235, 139-143.

      6. Zetler G (1985). Caerulein and its analogues: neuropharmacological properties. Peptides, 6, Suppl 3, 33-46.

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