title: Osmoregulatory thirst in mice lacking the transient receptor potential vanilloid type 1 (TRPV1) and/or type 4 (TRPV4) receptor.
abstract: Recent studies suggest the ability of the central nervous system to detect changes in osmolality is mediated by products of the genes encoding the transient receptor potential vanilloid-1 (TRPV1) or vanilloid-4 (TRPV4) channel. The purpose of the present study was to determine whether deletion of TRPV1 and/or TRPV4 channels altered thirst responses to cellular dehydration in mice. Injection of 0.5 or 1.0 M NaCl produced dose-dependent increases in cumulative water intakes of wild-type (WT), TRPV1-/-, TRPV4-/-, and TRPV1-/-V4-/- mice. However, there were no differences in cumulative water intakes between WT versus any other strain despite similar increases in plasma electrolytes and osmolality. Similar results were observed after injection of hypertonic mannitol. This was a consistent finding regardless of the injection route (intraperitoneal vs. subcutaneous) or timed access to water (delayed vs. immediate). There were also no differences in cumulative intakes across strains after injection of 0.15 M NaCl or during a time-controlled period (no injection). Chronic hypernatremia produced by sole access to 2% NaCl for 48 h also produced similar increases in water intake across strains. In a final set of experiments, subcutaneous injection of 0.5 M NaCl produced similar increases in the number of Fos-positive nuclei within the organum vasculosum of the lamina terminalis and median preoptic nucleus across strains but significantly smaller number in the subfornical organ of WT versus TRPV1-/-V4-/- mice. Collectively, these findings suggest that TRPV1 and/or TRPV4 channels are not the primary mechanism by which the central nervous system responds to cellular dehydration during hypernatremia or hyperosmolality to increase thirst.
authors.affiliation: Department of Cellular and Molecular Physiology, and.
authors.forename: Brian
authors.initials: B
authors.lastname: Kinsman
authors.affiliation: Department of Cellular and Molecular Physiology, and.
authors.forename: James
authors.initials: J
authors.lastname: Cowles
authors.affiliation: Department of Cellular and Molecular Physiology, and.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Lay
authors.affiliation: Department of Cellular and Molecular Physiology, and.
authors.forename: Sarah S
authors.initials: SS
authors.lastname: Simmonds
authors.affiliation: Department of Neural and Behavioral Sciences, Pennsylvania State University College of Medicine, Hershey, Pennsylvania.
authors.forename: Kirsteen N
authors.initials: KN
authors.lastname: Browning
authors.affiliation: Department of Cellular and Molecular Physiology, and Department of Neural and Behavioral Sciences, Pennsylvania State University College of Medicine, Hershey, Pennsylvania sstocker@hmc.psu.edu.
authors.forename: Sean D
authors.initials: SD
authors.lastname: Stocker
mesh_terms: D000818:Animals; D004326:Drinking / Q000502:physiology*; D005786:Gene Expression Regulation / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D064587:Osmoregulation / Q000502:physiology*; D050916:TRPV Cation Channels / Q000235:genetics / Q000378:metabolism*; D013894:Thirst / Q000502:physiology*
chemical_list: D050916:TRPV Cation Channels; C493921:TRPV1 protein, mouse; C486576:Trpv4 protein, mouse
keywords: cellular dehydration; hypernatremia; organum vasculosum of the lamina terminalis; subfornical organ; water intake
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