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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2013/07/11 22:33:22」(JST)

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Ceruletide (INN), also known as cerulein or caerulein, is a ten amino acid oligopeptide that stimulates smooth muscle and increases digestive secretions. Ceruletide 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.

The tree frog Litoria caerulae, formerly named Hyla caerulae.

Ceruletide was discovered and its structure elucidated in 1967 by Australian and Italian scientists from dried skins of the Australian green tree frog (Litoria caerulea, formerly Hyla caerulea). Its amino acid sequence is Pglu-Gln-Asp-Tyr[SO₃H]-Thr-Gly-Trp-Met-Asp-Phe-NH₂.^[1]^[2]

Induction of pancreatitis[edit]

Ceruletide upregulates pancreatic acinar cell intercellular adhesion molecule-1 (ICAM-1) proteins through intracellular upregulation of NF-κB. Surface ICAM-1 in turn promotes neutrophil adhesion onto acinar cells enhancing pancreatic inflammation.^[3] In addition to promoting the inflammatory cell reaction to acinar cells, ceruletide induces pancreatitis through dysregulation of digestive enzyme production and cytoplasmic vacuolization, leading to acinar cell death and pancreatic edema. Ceruletide also activates NADPH oxidase, a source of reactive oxygen species contributing to inflammation, as well as the Janus kinase/signal transducer, another inflammation inducer.^[4]

References[edit]

^ A. Anastasi, V. Erspamer, and R. Endean (1967). "Isolation and structure of caerulein, an active decapeptide from the skin ofHyla caerulea". Experentia 23 (9): 699–700. doi:10.1007/BF02154119.
^ G. De Caro, R. Endean, V. Esparmer, and M. Roseghini (1968). "Occurrence of caerulein in extracts of the skin of Hyla caerulea and other Australian hylids". Br J of Pharmac Chemother 33 (1): 48–58. PMC 1570274. PMID 5660165.
^ V. Zaninovic, A. S. Gukovskaya, I. Gukovsky, M. Mouria and S. J. Pandol (2000). "Cerulein upregulates ICAM-1 in pancreatic acinar cells, which mediates neutrophil adhesion to these cells". Am J Physiol Gastrointest Liver Physiol 279 (4): G666–676. PMID 11005752.
^ H. Kim (2008). "Cerulein Pancreatitis: Oxidative Stress, Inflammation, and Apoptosis". Gut and liver 167 (2): 74–80. doi:10.5009/gnl.2008.2.2.74. PMC 2871591. PMID 20485614.

English Journal

Cystathionine-gamma-lyase gene silencing with siRNA in monocytes/macrophages protects mice against acute pancreatitis.

Badiei A1, Chambers ST2, Gaddam RR1, Fraser R1, Bhatia M3.
Applied microbiology and biotechnology.Appl Microbiol Biotechnol.2016 Jan;100(1):337-46. doi: 10.1007/s00253-015-6989-z. Epub 2015 Sep 28.
Hydrogen sulphide (H2S) is an endogenous inflammatory mediator produced by cystathionine-γ-lyase (CSE) in monocytes/macrophages. To determine the role of H2S and macrophages in inflammation, we used small interference RNA (siRNA) to target the CSE gene and investigated its effect in a mouse model o
PMID 26411454

Peripancreatic fat necrosis worsens acute pancreatitis independent of pancreatic necrosis via unsaturated fatty acids increased in human pancreatic necrosis collections.

Noel P1, Patel K1, Durgampudi C2, Trivedi RN1, de Oliveira C1, Crowell MD1, Pannala R1, Lee K3, Brand R4, Chennat J4, Slivka A4, Papachristou GI4, Khalid A4, Whitcomb DC4, DeLany JP4, Cline RA4, Acharya C2, Jaligama D2, Murad FM5, Yadav D4, Navina S6, Singh VP1.
Gut.Gut.2016 Jan;65(1):100-11. doi: 10.1136/gutjnl-2014-308043. Epub 2014 Dec 10.
BACKGROUND AND AIMS: Peripancreatic fat necrosis occurs frequently in necrotising pancreatitis. Distinguishing markers from mediators of severe acute pancreatitis (SAP) is important since targeting mediators may improve outcomes. We evaluated potential agents in human pancreatic necrotic collections
PMID 25500204

Caffeine protects against experimental acute pancreatitis by inhibition of inositol 1,4,5-trisphosphate receptor-mediated Ca2+ release.

Huang W1, Cane MC2, Mukherjee R3, Szatmary P3, Zhang X4, Elliott V5, Ouyang Y3, Chvanov M3, Latawiec D5, Wen L4, Booth DM2, Haynes AC6, Petersen OH7, Tepikin AV2, Criddle DN3, Sutton R5.
Gut.Gut.2015 Dec 7. pii: gutjnl-2015-309363. doi: 10.1136/gutjnl-2015-309363. [Epub ahead of print]
OBJECTIVE: Caffeine reduces toxic Ca2+ signals in pancreatic acinar cells via inhibition of inositol 1,4,5-trisphosphate receptor (IP3R)-mediated signalling, but effects of other xanthines have not been evaluated, nor effects of xanthines on experimental acute pancreatitis (AP). We have determined e
PMID 26642860

Japanese Journal

SEW2871 alleviates the severity of caerulein-induced acute pancreatitis in mice

, , , , , ,
Biological and Pharmaceutical Bulletin advpub(0), 2015
… The aim of this study was to explore the effect of SEW2871, a S1P1-selective agonist, on caerulein-induced AP in mice. … AP was induced by giving eight intraperitoneal injections of caerulein (50 μg/kg/h) at hourly intervals. … SEW2871 was administered by gavage, at a dose of 20mg/kg, at 0h and 12h after the first intraperitoneal injection of caerulein. …
NAID 130005068106

Down-Regulation of Tumor Necrosis Factor-Associated Factor 6 Is Associated with Progression of Acute Pancreatitis Complicating Lung Injury in Mice

, , , , , , , ,
The Tohoku Journal of Experimental Medicine 217(4), 279-285, 2009
… This study was performed to investigate the potential role of TRAF6 in the pathogenesis of AP and pancreatitis-associated acute lung injury using a mouse model of caerulein-induced AP (CAP). … CAP was induced by intraperitoneal injection of caerulein hourly for 7 times (50μg/kg), and control mice were treated with saline of the same volume. …
NAID 130004459744

Expression patterns of epiplakin1 in pancreas,pancreatic cancer and regenerating pancreas

Yoshida Tetsu,Shiraki Nobuaki,Baba Hideo,Goto Mizuki,Fujiwara Sakuhei,Kume Kazuhiko,Kume Shoen,クメショウエン,クメカズヒコ,粂昭苑,粂和彦
Genes to cells 13(7), 667-678, 2008-07
… In addition, the expansion of Eppk1-positive cells occurs in a caerulein-induced acute pancreatitis, an acinar cell regeneration model. …
NAID 120002468595

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★リンクテーブル★

リンク元	「cerulein」

「cerulein」

Ceruletide
Systematic (IUPAC) name
	(3S)-3-{[(1S)-1-carbamoyl-2-phenylethyl]carbamoyl}-3-[(2S)-2-[(2S)-2-{2-[(3R)-2-[(2S)-2-[(2S)-2-[(2S)-4-carbamoyl-2-{[(2S)-5-oxopyrrolidin-2-yl]formamido}butanamido]-3-carboxypropanamido]-3-[4-(sulfooxy)phenyl]propanamido]-3-hydroxybutanamido]acetamido}-3-(1H-indol-3-yl)propanamido]-4-(methylsulfanyl)butanamido]propanoic acid
Clinical data
AHFS/Drugs.com	International Drug Names
Pregnancy cat.	?
Legal status	?
Identifiers
CAS number	17650-98-5
ATC code	V04CC04
PubChem	CID 16219178
ChemSpider	147304
UNII	888Y08971B
KEGG	D03442
ChEMBL	CHEMBL1201355
Chemical data
Formula	C58H73N13O21S2
Mol. mass	1352.40 g/mol
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関: caerulein、ceruletide

[1] A. Anastasi, V. Erspamer, and R. Endean (1967). "Isolation and structure of caerulein, an active decapeptide from the skin ofHyla caerulea". Experentia 23 (9): 699–700. doi:10.1007/BF02154119.

[2] G. De Caro, R. Endean, V. Esparmer, and M. Roseghini (1968). "Occurrence of caerulein in extracts of the skin of Hyla caerulea and other Australian hylids". Br J of Pharmac Chemother 33 (1): 48–58. PMC 1570274. PMID 5660165.

[3] V. Zaninovic, A. S. Gukovskaya, I. Gukovsky, M. Mouria and S. J. Pandol (2000). "Cerulein upregulates ICAM-1 in pancreatic acinar cells, which mediates neutrophil adhesion to these cells". Am J Physiol Gastrointest Liver Physiol 279 (4): G666–676. PMID 11005752.

[4] H. Kim (2008). "Cerulein Pancreatitis: Oxidative Stress, Inflammation, and Apoptosis". Gut and liver 167 (2): 74–80. doi:10.5009/gnl.2008.2.2.74. PMC 2871591. PMID 20485614.

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caerulein