Molecular Mechanisms of Antidiuretic Effect of Oxytocin

Abstract

Oxytocin is known to have an antidiuretic effect, but the mechanisms underlying this effect are not completely understood. We infused oxytocin by osmotic minipump into vasopressin-deficient Brattleboro rats for five days and observed marked antidiuresis, increased urine osmolality, and increased solute-free water reabsorption. Administration of oxytocin also significantly increased the protein levels of aquaporin-2 (AQP2), phosphorylated AQP2 (p-AQP2), and AQP3 in the inner medulla and in the outer medulla plus cortex. Immunohistochemistry demonstrated increased AQP2 and p-AQP2 expression and trafficking to the apical plasma membrane of principal cells in the collecting duct, and increased AQP3 expression in the basolateral membrane. These oxytocin-induced effects were blocked by treatment with the vasopressin V2 receptor antagonist SR121463B, but not by treatment with the oxytocin receptor antagonist GW796679X. We conclude that vasopressin V2 receptors mediate the antidiuretic effects of oxytocin, including increased expression and apical trafficking of AQP2, p-AQP2, and increased AQP3 protein expression. 19: 225-232, 200819: 225-232, . doi: 10.1681 In recent years, the understanding of the molecular basis for the antidiuretic effect of vasopressin has been substantially advanced. The vasopressin V2 receptor 1 and renal aquaporin (AQP) water channels 2 have been cloned. Vasopressin has been shown to mediate both long-and short-term effects on AQP2 in the principal cells of the collecting duct. The long-term effect of vasopressin leads to increased expression of AQP2, whereas the shortterm effects involve trafficking of AQP2 to the apical membrane of the principal cells. 3 There is also evidence that vasopressin increases AQP3 protein expression on the basolateral membrane of the principal cells 4 and up-regulates the Na-K-2Cl cotransporter, 5 the initiator of the countercurrent concentrating mechanism. J Am Soc NephrolOxytocin (OT) is also known to possess antidiuretic properties. 6 In this regard, use of OT to induce labor in pregnancy has been associated with water retention and hyponatremia. 7 OT has been shown in vitro to increase osmotic water transport in microdissected renal inner medullary collecting ducts (IMCD) 8 and in vivo to cause an antidiuresis in vasopressin-deficient Brattleboro rats. 9,10 These effects were reversed by a vasopressin V2 receptor antagonist, suggesting that OT stimulation of vasopressin receptors mediates the antidiuresis. These in vitro observations were not altered by two different OT receptor antagonists. 8 The effect of OT on the long-and short-term regulation of AQP2 or the expression of AQP3 and Na-K-2Cl cotransporter has not been studied. The present study was therefore undertaken to advance the knowledge at the

Unduly Enhanced Response to Tolvaptan in a Woman Showing Syndrome of Inappropriate Antidiuretic Hormone Secretion: An Investigation of Possible Causes

“…AVP increases water permeability along the collecting duct by binding the V2 receptor which, in turn, triggers short-term upregulation of the AQP2 water channel and long-term AQP2 protein transcription. In addition, the role of OXT in inducing SIADH was suggested by two (now dated) reports of water intoxication following OXT infusion (8,9) and by a more recent experimental study (10) that demonstrated that OXT can bind the V2 receptor and stimulate water permeability of the collecting duct and that its effect can be blocked by a V2 receptor inhibitor. However, neither agonists of V2R (AVP and OXT) nor the molecules involved in signal transduction (V2R and AQP2) revealed any genetic abnormalities.…”

The role of hyponatremia in preeclampsia

“…Additionally AVP metabolism is significantly changed in pregnancy. All of these lead to in a decrease in serum sodium concentration and serum osmolality by approximately 5 mEq/L and 10 mOsm/kg, respectively [21][22][23]. Although mild hyponatremia is part of the normal physiology of pregnancy, other factors may exacerbate this decline in serum sodium levels such as sodium restriction, polydipsia or inappropriate hypotonic intravenous fluid therapy [11,17].…”

Downregulation of UT-A1/UT-A3 Is Associated with Urinary Concentrating Defect in Glucocorticoid-Excess State

“…17 Kidneys were dissected on ice into OMϩC and IM regions. Tissue samples were immediately homogenized in a glass homogenizer at 4°C.…”