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The Molecular Structure of the Antidiuretic Hormone Elicited Water Channel

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Title: The Molecular Structure of the Antidiuretic Hormone Elicited Water Channel
Authors: Paredes, A.; Zeidel, Mark L.; Harris, H. William
Publisher: Pediatric Nephrology
Date Published: October 01, 1993
Reference Number: 267
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Measurements of osmotic water permeability (Pf) have shown that the plasma membranes of human red cells and certain epithelial cells possess specialized water channels. Although these water channels have been characterized extensively using biophysical techniques, the proteins that compose these unique channels have only recently been identified. Antidiuretic hormone (ADH) stimulation rapidly increases collecting duct epithelial cell Pf by fusion of water channel-containing vesicles (WCV) with their apical membranes. The proteins of WCV from toad bladder and rodent kidney have been characterized. The principal proteins in toad bladder WCV are 55,000 daltons (55 kDa) and 53 kDa and span the lipid bilayer of these vesicles. Polyclonal antisera raised against the 55-kDa and 53-kDa proteins inhibit ADH-stimulated toad bladder Pf by 80% and recognize protein bands of 46, 38 and 30 kDa in mouse kidney. Purification of WCV from rat kidney reveals enrichment of the 46-kDa protein. Recently, a 28-kDa integral membrane protein (called CHIP-28) has been isolated from human red cells. It forms functional water channels in Xenopus oocytes and when reconstituted into proteoliposomes. Large amounts of CHIP-28 protein are present in epithelial cells of the proximal tubule and descending thin limb of Henle's loop. Molecular cloning efforts are underway to elucidate the structure and function of these candidate water channel proteins.

This translation by the NDI Foundation is to assist the lay reader. To provide a clear, accessible interpretation of the original article, we eliminated or simplified some technical detail and complicated scientific language. We concentrated our translation on those aspects of the article dealing directly with NDI. The NDI Foundation thanks the researchers for their work toward understanding and more effectively treating this disorder.
© Copyright NDI Foundation 2007 (JC)

The plasma membranes of human red blood cells and the membranes of specific epithelial cells contain water channels (WC), molecular structures that, when inserted into the membranes, allow water to flow through. (Epithelium is the covering of external and internal body surfaces. It consists of cells joined by small amounts of cementing substances.) The water channels found in the red blood cells (CHIP-28 WCs) and those found in epithelia (ADH WCs) have similarities. Both require a low energy input. Both primarily allow only water to flow through them. (Epithelial WCs allow some protons to pass through, red blood cell WCs much less so.) The function of both is inhibited by mercury.

However, the proteins that comprise the two WCs are different. Harris, et al., discovered two proteins, identified by their molecular mass as 55 kDa and 53 kDa, that are major components of the ADH WC in toad bladder. And the major protein comprising the red blood cell WC ,CHIP-28, is a 28 kDa protein.

Researchers are currently attempting to clone WC proteins found in parts of the kidney called the proximal tubule and the collecting tubule, as well as those found in toad bladder granular cells. This will provide the basis for research which will provide insights into the most basic aspects of nephrology and physiology.