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Deletion of Both Transient Receptor Potential Vanilloid‐1 (TRPV1) and TRPV4 Genes Disrupts Osmoregulatory Thirst and Central Fos Activation
Author(s) -
Bardgett James,
Taylor A Caitlynn,
Bardgett Megan E,
McCarthy John J,
Stocker Sean D
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.605.5
Subject(s) - subfornical organ , trpv4 , medicine , thirst , endocrinology , osmoregulation , trpv1 , chemistry , transient receptor potential channel , nociceptin receptor , median preoptic nucleus , hypovolemia , lamina terminalis , wild type , hypernatremia , plasma osmolality , receptor , sodium , vasopressin , biology , central nervous system , gene , angiotensin ii , biochemistry , mutant , opioid , ecology , salinity , organic chemistry , opioid peptide
Recent evidence suggests that TRPV1 and TRPV4 channels are the putative link between plasma hypernatremia and brain osmosensation. However, deletion of either gene does not profoundly disrupt osmoregulatory responses, thereby raising the possibility that the other gene compensates to permit normal osmoregulation. Therefore, we hypothesized that mice lacking both TRPV1 and TRPV4 genes (TRPV1xV4‐/‐, n=9) vs wild‐type (n=10) mice would have attenuated thirst responses to plasma hypernatremia. Injection (0.5mL, sc) of 0.5 M NaCl produced smaller increases in water intake of TRPV1xV4‐/‐ vs wild‐type mice (0.37±0.02 vs 0.49±0.03mL, P<0.05). TRPV1xV4‐/‐ vs wild‐type mice also ingested less water after chronic salt loading by sole access to 2% NaCl for 48 hrs (0.06±0.03 vs 0.24±0.04mL, P<0.01). Yet, hypovolemia produced by 30% polyethylene glycol (0.5mL, sc) produced similar increases in water intake between TRPV1xV4‐/‐ vs wild‐type mice (0.67±0.04 vs 0.72±0.09mL). In addition, TRPV1xV4‐/‐ vs wild‐type mice displayed smaller numbers of Fos‐positive nuclei in brain osmosensory regions after injection of 0.5 M NaCl: organum vasculosum of the lamina terminalis (15±3 vs 33±6, P<0.05) and subfornical organ (4±2 vs 27±4, P<0.05). These findings suggest that TRPV1 and TRPV4 channels act in concert to participate in osmoregulation. Supported by NIH HL090826, AHA 0630202N & 0815372D