title: Apelin counteracts vasopressin-induced water reabsorption via cross talk between apelin and vasopressin receptor signaling pathways in the rat collecting duct.
abstract: Apelin receptors (ApelinRs) are expressed along an increasing cortico-medullary gradient in collecting ducts (CDs). We showed here that iv injection of apelin 17 (K17F) in lactating rats characterized by increases in both synthesis and release of arginine vasopressin (AVP) increased diuresis concomitantly with a significant decrease in urine osmolality and no change in Na(+) and K(+) excretion. Under these conditions, we also observed a significant decrease in apical aquaporin-2 immunolabeling in CD, with a cortico-medullary gradient, suggesting that K17F-induced diuresis could be linked to a direct action of apelin on CD. We then examined the potential cross talk between V1a AVP receptor (V1a-R), V2 AVP receptor (V2-R) and ApelinR signaling pathways in outer medullary CD (OMCD) and inner medullary CD microdissected rat CD. In OMCD, expressing the 3 receptors, K17F inhibited cAMP production and Ca(2+) influx induced by 1-desamino-8-D-arginine vasopressin a V2-R agonist. Similar effects were observed in inner medullary CD expressing only V2-R and ApelinR. In contrast, in OMCD, K17F increased by 51% the Ca(2+) influx induced by the stimulation of V1a-R by AVP in the presence of the V2-R antagonist SR121463B, possibly enhancing the physiological antagonist effect of V1a-R on V2-R. Thus, the diuretic effect of apelin is not only due to a central effect by inhibiting AVP release in the blood circulation as previously shown but also to a direct action of apelin on CD, by counteracting the antidiuretic effect of AVP occurring via V2-R.
authors.affiliation: Centre Interdisciplinaire de Recherche en Biologie (CIRB) (A.H.-C., L.B., A.F., F.J., C.L.-C.), Collège de France, 75005 Paris, France; Inserm Unit 1050 (A.H.-C., L.B., A.F., F.J., C.L.-C.), 75005 Paris, France; Université Pierre et Marie Curie (A.H.-C., L.B., A.F., F.J., N.B., C.L.-C.), 75005 Paris, France; Unité Mixte de Recherche Scientifique (UMRS) 1138 (N.B.), Centre de Recherche des Cordeliers, 75005 Paris, France; and Université Paris Descartes (N.B.), 75005 Paris, France.
authors.forename: Annette
authors.initials: A
authors.lastname: Hus-Citharel
authors.forename: Laurence
authors.initials: L
authors.lastname: Bodineau
authors.forename: Alain
authors.initials: A
authors.lastname: Frugière
authors.forename: Fanny
authors.initials: F
authors.lastname: Joubert
authors.forename: Nadine
authors.initials: N
authors.lastname: Bouby
authors.forename: Catherine
authors.initials: C
authors.lastname: Llorens-Cortes
mesh_terms: D065567:Absorption, Physiological / Q000187:drug effects*; D000818:Animals; D000073861:Apelin; D000075244:Apelin Receptors; D051399:Aquaporin 2 / Q000378:metabolism; D004231:Diuresis / Q000187:drug effects; D036341:Intercellular Signaling Peptides and Proteins / Q000494:pharmacology*; D007685:Kidney Tubules, Collecting / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D020239:Receptor Cross-Talk / Q000502:physiology; D043562:Receptors, G-Protein-Coupled / Q000502:physiology*; D017483:Receptors, Vasopressin / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects; D014667:Vasopressins / Q000037:antagonists & inhibitors*; D014867:Water / Q000378:metabolism*
chemical_list: D000073861:Apelin; D000075244:Apelin Receptors; C498579:Apln protein, rat; C491284:Aplnr protein, rat; C496025:Aqp2 protein, rat; D051399:Aquaporin 2; D036341:Intercellular Signaling Peptides and Proteins; D043562:Receptors, G-Protein-Coupled; D017483:Receptors, Vasopressin; D014867:Water; D014667:Vasopressins