Systems Biology of the Vasopressin V2 Receptor: New Tools for Discovery of Molecular Actions of a GPCR

Lihe Chen, Hyun Jun Jung, Arnab Datta, Euijung Park, Brian G. Poll, Hiroaki Kikuchi, Kirby T. Leo, Yash Mehta, Spencer Lewis, Syed J. Khundmiri, Shaza Khan, Chung Lin Chou, Viswanathan Raghuram, Chin Rang Yang, Mark A. Knepper

Research output: Contribution to journalArticlepeer-review


Systems biology can be defined as the study of a biological process in which all of the relevant components are investigated together in parallel to discover the mechanism. Although the approach is not new, it has come to the forefront as a result of genome sequencing projects completed in the first few years of the current century. It has elements of large-scale data acquisition (chiefly next-generation sequencing-based methods and protein mass spectrometry) and large-scale data analysis (big data integration and Bayesian modeling). Here we discuss these methodologies and show how they can be applied to understand the downstream effects of GPCR signaling, specifically looking at how the neurohypophyseal peptide hormone vasopressin, working through the V2 receptor and PKA activation, regulates the water channel aquaporin-2. The emerging picture provides a detailedframework for understanding the molecular mechanisms involved in water balance disorders, pointing the way to improved treatment of both polyuric disorders and water-retention disorders causing dilutional hyponatremia.

Original languageEnglish (US)
Pages (from-to)595-616
Number of pages22
JournalAnnual Review of Pharmacology and Toxicology
StatePublished - Jan 6 2022


  • diabetes insipidus
  • hyponatremia
  • kidney
  • next-generation DNA sequencing
  • protein mass spectrometry
  • syndrome of inappropriate antidiuresis

ASJC Scopus subject areas

  • Toxicology
  • Pharmacology


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