Reciprocal Regulation of Plasma Apelin and Vasopressin by Osmotic Stimuli

Abstract

Apelin is a neuropeptide that co-localizes with vasopressin (AVP) in magnocellular neurons and is involved in body fluid homeostasis. Osmotic stimuli have opposite effects on the regulation of apelin and AVP secretion in animal models, but whether this is true in humans is unknown. This study investigated the relationship among osmolality, apelin, and AVP in 10 healthy men after infusion of hypertonic saline or loading with water to increase and decrease plasma osmolality, respectively. Increasing plasma osmolality was accompanied by a parallel, linear increase in plasma AVP concentration and by a decrease in plasma apelin concentration. In contrast, decreasing plasma osmolality by water loading reduced plasma AVP concentration and rapidly increased plasma apelin concentration. These findings suggest that regulation of apelin secretion contributes to the maintenance of body fluid homeostasis. The osmotic pressure of body fluids is maintained within a remarkably narrow range in healthy adults. Body fluid homeostasis depends on neuronal pathways bearing very sensitive osmoreceptors, 1 located along the lamina terminalis, including the circumventricular organs, such as the subfornical organ and the organum vasculosum of the lamina terminalis as well as the median preoptic nucleus. 2 The subfornical organ and organum vasculosum of the lamina terminalis are neuronally interconnected with each other as well as with the median preoptic nucleus and the hypothalamic paraventricular and supraoptic nuclei. 3 These neuronal pathways convert small changes in osmolality into a neuronal signal to neurons that influence sensations of thirst and systemic arginine vasopressin (AVP) release, 2 thereby adjusting the intake or output of water to counteract changes in solute concentration. 4,5 A recently discovered peptide, apelin, may also play a major role in the maintenance of body fluid homeostasis. Apelin, initially isolated from bovine stomach extracts, 6 is the endogenous ligand of the human orphan G protein-coupled receptor APJ (putative receptor protein related to the angiotensin receptor AT1). 6,7 It is a 36 -amino acid peptide (apelin 36) derived from a single 77-amino acid precursor, proapelin. 6,8,9 Proapelin has a fully conserved C-terminal 17-amino acid sequence, apelin 17 (K17F), including the pyroglutamyl form of apelin 13 (pE13F). K17F and pE13F both are present in rat brain and plasma, 10 and apelin 36 is present in testis and uterus. 11 All peptides exhibit a high affinity for the human 8,12,13 and the rat apelin receptors. 14 Apelin possesses various cardiovascular functions (for reviews, [15][16][17] ). Apelin and its receptor have been detected in the endothelial cells of large conduit arteries, coronary vessels, and the endocar-

Apelin: an antithrombotic factor that inhibits platelet function

“…Expression of apelin and APJ receptor in human and mouse platelets: role in platelet aggregation Altered platelet function [1][2][3] and apelin levels 4,[11][12][13][14] are associated with various cardiovascular diseases. Therefore, we investigated whether apelin could act on platelet function.…”

“…[11][12][13] Nevertheless, their expression levels seem to vary significantly depending on tissues and cell types. Indeed, whereas apelin-13, apelin-17, and (Pyr1)apelin-13 are the predominant isoforms in plasma, [14][15][16] apelin-36 is the major isoform in colostrum. 17 In the present study, we show that apelin plays a key role in the regulation of platelet activation mainly induced by collagen and The online version of this article contains a data supplement.…”

The apelin receptor APJ: journey from an orphan to a multifaceted regulator of homeostasis

“…The latter is also the predominant form in rat whole brain and plasma ) and in human cardiac tissue ), while apelin-17 is present at a lower level in the rat hypothalamus and plasma . In human plasma, all three isoforms, apelin-13, (Pyr 1 )apelin-13 and apelin-17, are present (Reaux et al 2002, Azizi et al 2008. In Chinese hamster ovary (CHO) cells engineered to express the cloned human APJ, apelin-13 binds with high affinity to and associates with APJ more efficiently than apelin-36 and rapidly dissociates from APJ (Hosoya et al 2000).…”

Biased Signaling Favoring Gi over β-Arrestin Promoted by an Apelin Fragment Lacking the C-terminal Phenylalanine

“…The N-terminal glutamine residue of apelin 13 is pyroglutamylated, producing the pyroglutamyl form of apelin 13 (pGlu-Arg-Pro-Arg-LeuSer-His-Lys-Gly-Pro-Met-Pro-Phe, pE13F) (1,6,7). K17F and pE13F are the predominant molecular forms of apelin found in rat brain and in rat and human plasma (8,9). They exhibit high affinity (subnanomolar) for the human and the rat apelin receptors (ApelinR), although K17F has a 10-fold higher affinity than pE13F for both receptors (10 -12).…”

“…Central injection of K17F in lactating rats inhibits the phasic electrical activity of AVP neurons, thereby decreasing AVP release into the bloodstream and thus increasing aqueous diuresis (9). Moreover, plasma AVP and apelin levels are conversely regulated by osmotic and volemic stimuli in humans and rodents to maintain body fluid homeostasis (8,9,19,20).…”