BACKGROUND: Vasopressin V1a receptor (V1aR) null mice have insufficient acid-base balance, but the target cell for V1aR signaling which results in the urinary acidification has not been identified. METHODS: By using a quantitative in situ hybridization technique and a double-staining technique with an anti-AQP3 antibody in mice, we investigated the axial distribution and acidosis-induced expression of V1aR mRNA along the nephron. We also investigated the acidosis-induced morphological change in the tubule cells from wild-type and V1aR-null (V1aR(-/-)) mice. RESULTS: In the normal condition, V1aR mRNA was moderately expressed in the medullary thick ascending limb (MTAL) and highly expressed in the intercalated cell (IC) throughout the collecting duct (CD). However, no expression was observed in the proximal tubule, thin limbs of Henle's loop, and the principal cell of the CD. Importantly, V1aR mRNA was upregulated significantly both in the TAL and the IC of the CD in the inner stripe of the outer medulla (MTALis and IC of OMCDis, respectively) when mice were treated with NH4Cl (0.28 mol/L) for 6 days. Acidosis-induced hypertrophy, which was completely attenuated in V1aR(-/-) mice, was observed only in the IC of OMCDis (P < 0.005). In addition, urinary excretion of ammonia (NH3/NH4 (+)) was significantly decreased on day 3 (P < 0.05) and day 6 (P < 0.005) in the V1aR(-/-) mice treated with NH4Cl. CONCLUSION: In conclusion, the IC of OMCDis may be the target cell stimulated by the vasopressin V1aR axis and contribute to urinary acidification, at least during metabolic acidosis.
BACKGROUND:Vasopressin V1a receptor (V1aR) null mice have insufficient acid-base balance, but the target cell for V1aR signaling which results in the urinary acidification has not been identified. METHODS: By using a quantitative in situ hybridization technique and a double-staining technique with an anti-AQP3 antibody in mice, we investigated the axial distribution and acidosis-induced expression of V1aR mRNA along the nephron. We also investigated the acidosis-induced morphological change in the tubule cells from wild-type and V1aR-null (V1aR(-/-)) mice. RESULTS: In the normal condition, V1aR mRNA was moderately expressed in the medullary thick ascending limb (MTAL) and highly expressed in the intercalated cell (IC) throughout the collecting duct (CD). However, no expression was observed in the proximal tubule, thin limbs of Henle's loop, and the principal cell of the CD. Importantly, V1aR mRNA was upregulated significantly both in the TAL and the IC of the CD in the inner stripe of the outer medulla (MTALis and IC of OMCDis, respectively) when mice were treated with NH4Cl (0.28 mol/L) for 6 days. Acidosis-induced hypertrophy, which was completely attenuated in V1aR(-/-) mice, was observed only in the IC of OMCDis (P < 0.005). In addition, urinary excretion of ammonia (NH3/NH4 (+)) was significantly decreased on day 3 (P < 0.05) and day 6 (P < 0.005) in the V1aR(-/-) mice treated with NH4Cl. CONCLUSION: In conclusion, the IC of OMCDis may be the target cell stimulated by the vasopressin V1aR axis and contribute to urinary acidification, at least during metabolic acidosis.
Authors: Monica Carmosino; Heddwen L Brooks; Qi Cai; Linda S Davis; Susan Opalenik; Chuanming Hao; Matthew D Breyer Journal: Am J Physiol Renal Physiol Date: 2006-07-11
Authors: T Tanabe; T Nukada; Y Nishikawa; K Sugimoto; H Suzuki; H Takahashi; M Noda; T Haga; A Ichiyama; K Kangawa Journal: Nature Date: 1985 May 16-22 Impact factor: 49.962