Apelin Counteracts Vasopressin-Induced Water Reabsorption via Cross Talk Between Apelin and Vasopressin Receptor Signaling Pathways in the Rat Collecting Duct

作者：Hus Citharel Annette; Bodineau Laurence; Frugiere Alain; Joubert Fanny; Bouby Nadine; Llorens Cortes Catherine^*

来源：Endocrinology, 2014, 155(11): 4483-4493.

DOI：10.1210/en.2014-1257

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 V-1a AVP receptor (V-1a-R), V-2 AVP receptor (V-2-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 Ca2+ influx induced by 1-desamino-8-D-arginine vasopressin a V-2-R agonist. Similar effects were observed in inner medullary CD expressing only V-2-R and ApelinR. In contrast, in OMCD, K17F increased by 51% the Ca2+ influx induced by the stimulation of V-1a-R by AVP in the presence of the V-2-R antagonist SR121463B, possibly enhancing the physiological antagonist effect of V-1a-R on V-2-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 V-2-R.

• 出版日期2014-11