Caerulein is a peptide secreted from the skin of frogs.
Caerulein shares the conserved C-terminal sequence that is
responsible for receptor activation with vertebrate gastrin
and 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 blood
pressure and extravascular smooth muscle contraction
in mammals. Caerulein was first purified from the Australian tree frog Hyla caerulea in 1967.
Caerulein is a decapeptide that contains the C-terminal
four 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 and
preproCPF-St7, have been reported in the western clawed
frog Silurana tropicalis. The precursor contains a signal peptide, an antimicrobial peptide called a
caerulein precursor fragment (CPF), and mature caerulein. Caerulein has been identified in various
frog species, including Xenopus laevis, Litoria splendida,
and Hylambates maculatus. Sauvage’s leaf frog, Phyllomedusa sauvagei, possesses a caerulein-like nonapeptide
called phyllocaerulein. These peptides share the
C-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 in
DMSO, but insoluble in acetone and diethyl ether.
Gene, mRNA, and precursor
In S. tropicalis, two caerulein precursor genes have
been identified, and they have a four-exon structure. Two caerulein mRNAs are 428 and 418 bases in length
and encode precursors of 98 and 91 aa residues,
respectively.
In X. laevis, a caerulein-like substance is released in
response to adrenaline treatment. This substance stimulates the contraction of the guinea pig gall bladder and
pancreatic secretions in rats. Amino acid analysis of
the secreted substance shows a similar aa composition
to that of caerulein. Seasonal changes in caerulein synthesis have been reported. For example, L. splendida synthesizes caerulein during the reproductive season in
summer. In winter, the synthesis of caerulein is less
active. Also, the desulfated form of caerulein increases
and caerulein 1.2, which has relatively low biological
activity, is released.
Treatment of the outside of frog skin with caerulein
results in an influx of sodium ions while treatment of
the inside of frog skin represses sodium ion influx. These
results suggest that caerulein is associated with the maintenance of sodium ion levels in the dermal cells. In addition, preprocaerulein contains antimicrobial CRF, and
caerulein can affect gastrin and CCK signaling in other
animals. These suggest that CRF and caerulein may function as defensive peptides against microbes and predators in the frog.
Caerulein is used to generate rodent models of pancreatitis. Caerulein acts as an agonist of CCK1R and CCK2R
because of its structural similarity to gastrin and CCK.
Treatment with a high dose of caerulein induces the
secretion of pancreatic juice and results in acute pancreatitis in rodents.
Ceosunin,Kyowa Hakko,Japan,1976
Stimulant (gastric secretory).
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.
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 gastrointes
inal 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.
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 the
threonyl radical blocked by an acyl radical in a suitable solvent, such as
dimethylformamide, 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 radical
blocked by an acyl radical. The decapeptide (III) is treated, at low
temperature, with the complex anhydrous pyridine sulfuric anhydride finally to
obtain 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 sulfate
radical and the hydroxyl of the threonyl radical protected by an acyl radical.
Finally, by mild alkaline hydrolysis of the decapeptide (IV) one obtains the
decapeptide product.
Stimulant (gastric secretory)
A poison by
subcutaneous route. When heated to
decomposition it emits toxic vapors of NOx
and SOx
