Apelin, the natural ligand of the orphan receptor APJ, is abundantly secreted in the colostrum.
By using a strategy that we have developed to search for the ligands of orphan seven-transmembrane-domain receptors [S. Hinuma et al., Nature 393 (1998) 272-276], we have recently identified a natural ligand, apelin, for the orphan 7TMR, APJ [K. Tatemoto et al., Biochem. Biophys. Res. Commun. 251 (1998) 471-476]. In this paper, we isolated rat and mouse apelin cDNAs, and analyzed the tissue distribution of apelin mRNA in rats. Although apelin mRNA was widely detected in a variety of tissues, the highest expression of apelin mRNA was detected in the mammary gland of pregnant rats. In the mammary gland, biologically active apelin and its mRNA considerably increased during pregnancy and lactation, and reached a maximal level around parturition. Moreover, a large amount of apelin (14-93 pmol/ml) was found to be secreted in the bovine colostrum, and it was still detectable even in commercial bovine milk. Since apelin partially suppressed cytokine production by mouse spleen cells in response to T cell receptor/CD3 cross-linking, the oral intake of apelin in the colostrum and milk might modulate immune responses in neonates.
Habata
Y
Y
Discovery Research Laboratories 1, Pharmaceutical Discovery Research Division, Takeda Chemical Industries, Ltd., Wadai 10, Tsukuba, Ibaraki, Japan.
Fujii
R
R
Hosoya
M
M
Fukusumi
S
S
Kawamata
Y
Y
Hinuma
S
S
Kitada
C
C
Nishizawa
N
N
Murosaki
S
S
Kurokawa
T
T
Onda
H
H
Tatemoto
K
K
Fujino
M
M
D054392:Adipokines; D000595:Amino Acid Sequence; D000818:Animals; D000073861:Apelin; D000075244:Apelin Receptors; D016466:CHO Cells; D002352:Carrier Proteins / Q000138:chemical synthesis / Q000235:genetics / Q000378:metabolism*; D002417:Cattle; D005576:Colforsin; D003126:Colostrum / Q000378:metabolism*; D006224:Cricetinae; D000242:Cyclic AMP / Q000378:metabolism; D018076:DNA, Complementary / Q000302:isolation & purification; D005260:Female; D036341:Intercellular Signaling Peptides and Proteins; D007774:Lactation / Q000378:metabolism; D008024:Ligands; D008297:Male; D008321:Mammary Glands, Animal / Q000378:metabolism; D051379:Mice; D008892:Milk / Q000737:chemistry; D008969:Molecular Sequence Data; D011247:Pregnancy / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D017448:Receptors, Dopamine D2 / Q000737:chemistry / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled; D020133:Reverse Transcriptase Polymerase Chain Reaction
D054392:Adipokines; D000073861:Apelin; D000075244:Apelin Receptors; C402826:Apln protein, mouse; C498579:Apln protein, rat; C491285:Aplnr protein, mouse; C491284:Aplnr protein, rat; D002352:Carrier Proteins; D018076:DNA, Complementary; D036341:Intercellular Signaling Peptides and Proteins; D008024:Ligands; D012333:RNA, Messenger; D017448:Receptors, Dopamine D2; D043562:Receptors, G-Protein-Coupled; D005576:Colforsin; D000242:Cyclic AMP