Apelin, the natural ligand of the orphan receptor APJ, is abundantly secreted in the colostrum

Abstract

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.

The apelinergic system in the developing lung: Expression and signaling

“…Apelin-36 was the first of these shorter C-terminal sequences being described to bind and activate APJ [45]. Also Apelin-17, Apelin-13 and its pyroglutamyl isoform which is resistant to degradation, (Pyr1)-Apelin-13, were proven to act as functional ligands of APJ and in some cases exhibited much higher biological activity than Apelin-36 [45,17,18,25,46].…”

The apj receptor is expressed in pancreatic islets and its ligand, apelin, inhibits insulin secretion in mice

“…It was subsequently demonstrated to be ubiquitously expressed with high expression levels in the lung, heart, medial layer of vessels and endothelial cells (3,4). The receptor is a G-protein coupled receptor signaling inhibition of adenylyl cyclase activity eliciting reduced cAMP formation (1,5) although also raise of intracellular calcium and activation of extracellularly regulated kinases (ERK) have been reported (6,7). The endogenous ligand for the apj receptor is apelin, which was initially demonstrated in stomach extracts in 1998 (8).…”

“…The endogenous ligand for the apj receptor is apelin, which was initially demonstrated in stomach extracts in 1998 (8). Later studies have shown that apelin mRNA is expressed in several tissues, as for example in several regions in the CNS, in the heart, lung, placenta, mammary gland and gastrointestinal tract (3,5,(9)(10)(11).…”

“…However, multiple apelin forms exist consisting of 13, 16 and 17 amino acids with the C-terminal end identical in all forms (13); in fact, the C-terminal end is highly conserved across species (5).…”

L’apéline, un inhibiteur naturel de l’effet antidiurétique de la vasopressine

“…Ces données peuvent expliquer la présence de deux transcrits de taille différente, de 3,0 et 3,5 kb, en proportions variables suivant les tissus étudiés [7]. La proapéline a été isolée dans différentes espèces [5][6][7] et l'alignement des séquences de souris, rat, boeuf et homme a révélé une conservation stricte des 17 derniers acides aminés carboxyterminaux correspondant à l'apéline-17 ou K17F (Figure 1). In vivo, la proapéline donne naissance à différentes formes molé-culaires d'apéline : dans le cerveau et le plasma de rat, on retrouve majoritairement la forme pyroglutamyl de l'apéline 13, pE13F (Figure 1) et en plus faible quantité, K17F [8] ; dans le testicule et l'utérus, c'est l'apéline 36 qui prédomine, alors que, dans la glande mammaire, on retrouve à la fois l'apéline 36 et pE13F [9].…”