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1 Division of Nephrology, Vanderbilt University, Nashville, Tennessee, United States
2 Department of Physiology, University of Arizona, Tucson, Arizona, United States
3 Department of Pathology, Vanderbilt University, Nashville, Tennessee, United States
4 Nephrology/Medicine, Vanderbilt University, Nashville, TN, United States
* To whom correspondence should be addressed. E-mail: matthew.breyer{at}vanderbilt.edu.
Abstract. Vasopressin and vasopressin antagonists are finding expanded use in mouse models of disease and in clinical medicine. To provide further insight into the physiological role of V1a and V2 vasopressin receptors in the human and mouse kidney, intra-renal localization of the receptors mRNA was determined by in situ hybridization. V2 receptor mRNA was predominantly expressed in the medulla, whereas mRNA for V1a receptors predominated in the cortex. The segmental localization of vasopressin receptor mRNAs was determined using simultaneous in situ hybridization and immunohistochemistry for segment-specific markers including AQP2, DBA, ENaC, Tamm Horsfall glycoprotein and Thiazide--sensitive Na+/Cl- cotransporter (TSC). Notably V1aR expression was exclusively expressed in V--ATPase/AE1 labeled alpha intercalated cells of the medullary collecting duct in both mouse and human kidney. In cortical collecting ducts, V1a mRNA was more widespread and detected in both principal and intercalated cells. V2R mRNA is diffusely expressed along the collecting ducts in both mouse and human kidney, with higher expression levels in the medulla. These results demonstrate heterogenous axial expression of both V1a and V2 vasopressin receptors along the human and mouse collecting duct. The restricted expression of V1aR mRNA in intercalated cells suggest a role for this receptor in acid-base balance. These findings further suggest distinct regulation of renal transport function by AVP through V1a and V2 receptors in the cortex versus the medulla.
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