Vasopressin V1a receptor is required for nucleocytoplasmic transport of mineralocorticoid receptor.

Hori K, Nagai T, Izumi Y, Kimura M, Hasuike Y, Nakayama Y, Nanami M, Tokuyama M, Otaki Y, Kuragano T, Kohda Y, Obinata M, Kawahara K, Tanoue A, Tomita K, Nakanishi T, Nonoguchi H. Vasopressin V1a receptor is required for nucleocytoplasmic transport of mineralocorticoid receptor. Am J Physiol Renal Physiol 303: F1080-F1088, 2012. First published July 18, 2012; doi:10.1152/ajprenal.00052.2012.-We previously reported that a deficiency in the vasopressin V1a receptor (V1aR) results in type 4 renal tubular acidosis, which suggests that vasopressin exerts direct effects on the physiological actions of aldosterone. We investigated the role of vasopressin for nucleocytoplasmic transport of mineralocorticoid receptor (MR) in the intercalated cells. Vasopressin V1aR-deficient (V1aR(-/-)) mice showed largely decreased expression of MR and 11 beta-hydroxysteroid dehydrogenase type 2 (11 beta HSD2) in the medulla of the kidney, which was partially ameliorated by fludrocortisone treatment. The incubation of IN-IC cells, an intercalated cell line established from temperature-sensitive SV40 large T antigen-expressing rats, with aldosterone or vasopressin increased the nuclear-to-cytoplasmic ratio of the MR from 11.2 to 47.2% and from 18.7 to 61.2%, respectively, in 30 min without any changes in MR expression from the whole cell extract. The immunohistochemistry analysis of the IN-IC cells revealed the nuclear accumulation of MRs after a 30-min incubation with aldosterone or vasopressin. These effects were accompanied by an increase in regulator of chromosome condensation-1 (RCC-1) due to aldosterone and a decrease in Ran GTPase-activating protein 1 (Ran Gap1) due to vasopressin. RNA interference against V1aR abolished the nuclear accumulation of MR induced by aldosterone or vasopressin. Vasopressin increased PKC alpha and -beta(1) expression, and aldosterone increased PKC delta and -zeta expression, but these effects were abolished with a V1aR knockdown. These results suggest that vasopressin directly regulates the nucleocytoplasmic transport of MRs via the V1aR in the intercalated cells of the collecting ducts.