High magnesium concentration inhibits the effect of arginine vasopressin (AVP) on smooth muscle contraction and platelet aggregation and also influences hepatocyte AVP receptor binding. The aim of this study was to determine the role of magnesium concentration [Mg 2+ ] in AVP-stimulated water transport in the kidney collecting duct. The effect of low and high peritubular [Mg 2+ ] on the AVP-stimulated osmotic water permeability coefficient (P f ) was evaluated in the isolated perfused rabbit cortical collecting duct (CCD). Control tubules bathed and perfused with standard Ringer bicarbonate solution containing 1 mM Mg 2+ presented a P f of 223.9 ± 27.2 µm/s. When Mg 2+ was not added to the bathing solution, an increase in the AVPstimulated P f to 363.1 ± 57.2 µm/s (P<0.05) was observed. An elevation of Mg 2+ to 5 mM resulted in a decrease in P f to 202.9 ± 12.6 µm/ s (P<0.05). This decrease in the AVP-stimulated P f at 5 mM Mg 2+ persisted when the CCDs were returned to 1 mM Mg 2+ , P f = 130.2 ± 20.3 µm/s, and was not normalized by the addition of 8-[4-chlorophenylthio]-adenosine 3',5'-cyclic monophosphate, a cAMP analogue, to the preparation. These data indicate that magnesium may play a modulatory role in the action of AVP on CCD osmotic water permeability, as observed in other tissues. The collecting duct, as the final portion of the nephron, plays an important role in the control of the extracellular water and salt balance. During water deprivation or extracellular volume contraction, increases in vasopressin release elicit a rise in osmotic water permeability in the kidney collecting ducts. The effect of vasopressin on water reabsorption in the collecting duct is mediated through the classic second messenger adenosine 3',5'-cyclic monophosphate (cAMP) via V 2 receptors. The increase in cyclic AMP levels in the cell leads to the activation of protein kinase A, which promotes the phosphorylation and trafficking of water channels, i.e., the aquaporin-2 protein, from the intracellular vesicles to the plasma membrane (1,2).The hormone arginine vasopressin (AVP) has multiple functions in the organism, including the stimulation of kidney antidiure-
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