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      TRPV1-Mediated Diuresis and Natriuresis Induced by Hypertonic Saline Perfusion of the Renal Pelvis

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          Background: The transient receptor potential vanilloid type 1 (TRPV1) channel is known to be activated by multiple stimuli, albeit its role in mediating renal function is largely unknown. This study was designed to test the hypothesis that TRPV1 mediates diuresis and natriuresis induced by hypertonic saline perfusion into the pelvis. Methods: NaCl or KCl was perfused into the left renal pelvis of rats at a rate without changing renal pelvic pressure. Afferent renal nerve activity (ARNA), urine flow rate (V) and urinary sodium excretion (UNaV) in the presence or absence of selective antagonists of TRPV1, capsazepine (CAPZ), or neurokinin-1 (NK1) receptors, RP67580, were examined. Results: Unilateral renal pelvis perfusion of NaCl at 600 m M, but not 150 or 300 m M, increased ipsilateral ARNA and contralateral V and UNaV, which were blocked by ipsilateral administration of CAPZ or RP67580. In contrast, KCl perfused at 150 or 300 m M, but not 600 m M, increased ipsilateral ARNA and contralateral V and UNaV, which were insensitive to CAPZ. Conclusion: Unilateral hypertonic saline perfusion causes contralateral diuresis and natriuresis via TRPV1 or NK1 activation, indicating that these receptors may play a critical role in sensing microenvironmental changes in the renal pelvis to modulate renal function in health and disease.

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          Most cited references 15

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          OTRPC4, a nonselective cation channel that confers sensitivity to extracellular osmolarity.

          Ca2+-permeable channels that are involved in the responses of mammalian cells to changes in extracellular osmolarity have not been characterized at the molecular level. Here we identify a new TRP (transient receptor potential)-like channel protein, OTRPC4, that is expressed at high levels in the kidney, liver and heart. OTRPC4 forms Ca2+-permeable, nonselective cation channels that exhibit spontaneous activity in isotonic media and are rapidly activated by decreases in, and are inhibited by increases in, extracellular osmolarity. Changes in osmolarity of as little as 10% result in significant changes in intracellular Ca2+ concentration. We propose that OTRPC4 is a candidate for a molecular sensor that confers osmosensitivity on mammalian cells.
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            The Cloned Capsaicin Receptor Integrates Multiple Pain-Producing Stimuli

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              TRP channels: an overview.

              The TRP ("transient receptor potential") family of ion channels now comprises more than 30 cation channels, most of which are permeable for Ca2+, and some also for Mg2+. On the basis of sequence homology, the TRP family can be divided in seven main subfamilies: the TRPC ('Canonical') family, the TRPV ('Vanilloid') family, the TRPM ('Melastatin') family, the TRPP ('Polycystin') family, the TRPML ('Mucolipin') family, the TRPA ('Ankyrin') family, and the TRPN ('NOMPC') family. The cloning and characterization of members of this cation channel family has exploded during recent years, leading to a plethora of data on the roles of TRPs in a variety of tissues and species, including mammals, insects, and yeast. The present review summarizes the most pertinent recent evidence regarding the structural and functional properties of TRP channels, focusing on the regulation and physiology of mammalian TRPs.

                Author and article information

                Am J Nephrol
                American Journal of Nephrology
                S. Karger AG
                September 2007
                24 August 2007
                : 27
                : 5
                : 530-537
                Department of Medicine, the Neuroscience Program, and the Cell and Molecular Biology Program, Michigan State University, East Lansing, Mich., USA
                107665 Am J Nephrol 2007;27:530–537
                © 2007 S. Karger AG, Basel

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                Page count
                Figures: 5, Tables: 1, References: 29, Pages: 8
                Original Report: Patient-Oriented, Translational Research


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