| Discovery | Caerulein is a peptide secreted from the skin of frogs.Caerulein shares the conserved C-terminal sequence that isresponsible for receptor activation with vertebrate gastrinand cholecystokinin (CCK), and functions as their agonist. Caerulein was first described in a number of Australian amphibians as a polypeptide that stimulates pancreatic external secretion and elicits a decrease in bloodpressure and extravascular smooth muscle contractionin mammals. Caerulein was first purified from the Australian tree frog Hyla caerulea in 1967. |
| Structure | Caerulein is a decapeptide that contains the C-terminalfour aa sequence (Trp-Met-Asp-Phe-NH2) that is conserved in the vertebrate gastrin and CCK.A pyroglutamate residue is present in the N-terminus,and a C-terminal phenylalanine residue is amidated.Caerulein possesses a sulfated tyrosine at the seventh residue from the C-terminus. Two caerulein precursors, preproCPF-St6 andpreproCPF-St7, have been reported in the western clawedfrog Silurana tropicalis. The precursor contains a signal peptide, an antimicrobial peptide called acaerulein precursor fragment (CPF), and mature caerulein. Caerulein has been identified in variousfrog species, including Xenopus laevis, Litoria splendida,and Hylambates maculatus. Sauvage’s leaf frog, Phyllomedusa sauvagei, possesses a caerulein-like nonapeptidecalled phyllocaerulein. These peptides share theC-terminal four aa sequence. Caerulein 1.2 of the magnificent tree frog, Litoria splendida, does not have the consensus 4-aa sequence (Trp-Phe-Asn-Phe-NH2). Mr: H. caerulea caerulein, 1352. Caerulein is soluble inDMSO, but insoluble in acetone and diethyl ether.
|
| Gene, mRNA, and precursor | In S. tropicalis, two caerulein precursor genes havebeen identified, and they have a four-exon structure. Two caerulein mRNAs are 428 and 418 bases in lengthand encode precursors of 98 and 91 aa residues,respectively. |
| Synthesis and release | In X. laevis, a caerulein-like substance is released inresponse to adrenaline treatment. This substance stimulates the contraction of the guinea pig gall bladder andpancreatic secretions in rats. Amino acid analysis ofthe secreted substance shows a similar aa compositionto that of caerulein. Seasonal changes in caerulein synthesis have been reported. For example, L. splendida synthesizes caerulein during the reproductive season insummer. In winter, the synthesis of caerulein is lessactive. Also, the desulfated form of caerulein increasesand caerulein 1.2, which has relatively low biologicalactivity, is released. |
| Biological functions | Treatment of the outside of frog skin with caeruleinresults in an influx of sodium ions while treatment ofthe inside of frog skin represses sodium ion influx. Theseresults suggest that caerulein is associated with the maintenance of sodium ion levels in the dermal cells. In addition, preprocaerulein contains antimicrobial CRF, andcaerulein can affect gastrin and CCK signaling in otheranimals. These suggest that CRF and caerulein may function as defensive peptides against microbes and predators in the frog. |
| Clinical implications | Caerulein is used to generate rodent models of pancreatitis. Caerulein acts as an agonist of CCK1R and CCK2Rbecause of its structural similarity to gastrin and CCK.Treatment with a high dose of caerulein induces thesecretion of pancreatic juice and results in acute pancreatitis in rodents. |
| Originator | Ceosunin,Kyowa Hakko,Japan,1976 |
| Uses | Caerulein is a ten amino acid oligopeptide that stimulates smooth muscle and increases digestive secretions. It is similar in action and composition to cholecystokinin. It stimulates gastric, biliary, and pancreatic secretion; and certain smooth muscle. It is used in paralytic ileus and as diagnostic aid in pancreatic malfunction. It is used to induce pancreatitis in experimental animal models. |
| Uses | Stimulant (gastric secretory). |
| Definition | ChEBI: A decapeptide comprising 5-oxoprolyl, glutamyl, aspartyl, O-sulfotyrosyl, threonyl, glycyl, tryptopyl, methionyl, aspartyl and phenylalaninamide residues in sequence. Found in the skins of certain Australian amphibians, it is an analogue of the gastrointesinal peptide hormone cholecystokinin and stimulates gastric, biliary, and pancreatic secretion. It is used in cases of paralysis of the intestine (paralytic ileus) and as a diagnostic aid in pancreatic malfunction. |
| Manufacturing Process | The tetrapeptide, L-pyroglutamyl-L-glutaminyl-L-aspartyl-L-tyrosine-azide (I),is condensed with the hexapeptide, L-threonyl-glycyl-L-tryptophanyl-L-methionyl-L-aspartyl-L-phenylalaninamide (II), having the hydroxyl of thethreonyl radical blocked by an acyl radical in a suitable solvent, such asdimethylformamide, to obtain the decapeptide, L-pyroglutamyl-L-glutaminyl-L-aspartyl-L-tyrosyl-L-threonylglycyl-L-tryptophanyl-L-methionyl-L-aspartyl-Lphenylaninamide (III) having the hydroxy group of the threonyl radicalblocked by an acyl radical. The decapeptide (III) is treated, at lowtemperature, with the complex anhydrous pyridine sulfuric anhydride finally toobtain the decapeptide, L-pyroglutamyl-L-glutaminyl-L-aspartyl-L-tyrosyl-L-threonyl-glycyl-L-tryptophanyl-L-methionyl-L-aspartyl-L-phenylalaninamide(IV) having the phenolic group of the tyrosyl radical protected by a sulfateradical and the hydroxyl of the threonyl radical protected by an acyl radical.
Finally, by mild alkaline hydrolysis of the decapeptide (IV) one obtains thedecapeptide product. |
| Therapeutic Function | Stimulant (gastric secretory) |
| Hazard | A poison. |
| Safety Profile | A poison by subcutaneous route. When heated to decomposition it emits toxic vapors of NOx and SOx |
| storage | Store at -20°C |
