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Vasopressin and its Receptors

The chief factor that regulates water excretion by the kidney is the peptide hormone vasopressin. Vasopressin is secreted by the posterior pituitary gland. Under everyday circumstances, its circulating level is governed the tonicity of the extracellular fluid, increasing with increased plasma osmolality, e.g. in response to dehydration.Vasopressin has actions in multiple tissues, but its major effects are in the kidney where it decreases the excretion of water by increasing the osmotic transport of water from the renal collecting duct lumen to the blood.

The major focus of the Epithelial Systems Biology Laboratory (ESBL) is to understand the molecular mechanisms whereby vasopressin regulates osmotic water transport across the collecting duct epithelium. The regulation of water transport occurs by control of the molecular water channel aquaporin-2. Actions of vasopressin in the kidney are mediated by two G-protein coupled receptors, the V2 receptor (gene symbol: Avpr2) and the V1a receptor (Avpr1a). Much of the work in the ESBL is focused on the signaling network evoked by binding of vasopressin to the V2 receptor in renal collecting duct cells.

In a recent study, we used deep sequencing technology (RNA-seq) to identify and quantify every transcript expressed in each of the 14 renal tubule segments that make up the renal tubule (1). This study is an example of the use of systems biology techniques to study the function of the kidney. The distribution of transcripts coding for the vasopressin receptors and the related oxytocin receptor along the renal tubule are depicted in the table below.

Relative Transcript Abundance, RPKM

 Gene
 Symbol
RefSeq
ID
Prox S1. Prox S2. Prox S3. .DTL-1.. .DTL-2.. .DTL-3.. ..ATL... ..MTAL.. ..CTAL.. ..DCT .. ..CNT.. ..CCD.. ..OMCD. ..IMCD.
Avpr1a NM_053019 0 0 0 0.1 0 14.2 0.3 0 0 2.6 13.2 45.3 0.1 0
Avpr1b NM_017205 0 0 0 0 0 0 0 0 0 0 0 0 0 0
Avpr2 NM_019136 0.3 0.3 0.4 0.3 0.1 0.5 2.2 14.9 33.9 9.9 176.8 399.5 472.1 371.1
Oxtr NM_012871 0 0 0 0 0 0 0 0 1.2 0 0 0 0 0
Terminology: S1, 1st segment of proximal tubule (PT); S2, 2nd segment of PT; S3, 3rd segment of PT; DTL-1, short-loop thin descending limb of Henle; DTL-2, long-loop thin descending limb; DTL-3, long-loop thin descending limb; ATL, thin ascending limb of Henle; MTAL, medullary thick ascending limb of Henle; CTAL, cortical thick ascending limb; DCT, distal convoluted tubule; CNT, connecting tubule; CCD, cortical collecting duct; OMCD, outer medullary collecting duct; IMCD, inner medullary collecting duct.

References:

  1. Lee JW, Chou CL, Knepper MA. Deep Sequencing in Microdissected Renal Tubules Identifies Nephron Segment-Specific Transcriptomes. J Am Soc Nephrol. 2015; 26: 2669-77. PMID: 25817355.

  2. Miranda CA, Lee JW, Chou CL, Knepper MA. Tolvaptan as a tool in renal physiology. Am J Physiol Renal Physiol. 2014; 306: F359-66. PMID: 24305472.

  3. Hoffert JD, Pisitkun T, Saeed F, Wilson JL, Knepper MA. Global analysis of the effects of the V2 receptor antagonist satavaptan on protein phosphorylation in collecting duct. Am J Physiol Renal Physiol. 2014; 306: 410-21. PMID: 24259510.

  4. Hoffert JD, Pisitkun T, Saeed F, Song JH, Chou CL, Knepper MA. Dynamics of the G protein-coupled vasopressin V2 receptor signaling network revealed by quantitative phosphoproteomics. Mol Cell Proteomics. 2012; 11: M111.014613. PMID: 22108457.

  5. Rinschen MM, Yu MJ, Wang G, Boja ES, Hoffert JD, Pisitkun T, Knepper MA. Quantitative phosphoproteomic analysis reveals vasopressin V2-receptor-dependent signaling pathways in renal collecting duct cells. Proc Natl Acad Sci USA. 2010; 107: 3882-7. PMID: 20139300.