Role of Forebrain TRPV1 Receptors in Body Fluid Homeostasis

Abstract

Neurons of the organum vasculosum of the lamina terminalis mediate thirst and the secretion of antidiuretic hormone during hypernatremia. The osmosensitivity of these neurons is mediated by the transient receptor potential vanilloid‐type 1 (TRPV1) receptor. Therefore, we hypothesized that TRPV1 −/− versus wild‐type (WT) mice would have blunted thirst responses to osmotic dependent stimuli. TRPV1−/− versus WT mice ingested similar amounts of water after sc injection (0.5 ml) of 0.5 M NaCl (0.55±0.2 vs 0.53±0.03 mL) or 1.0 M NaCl (1.44±0.05 vs 1.25±0.05 mL). Overnight water deprivation produced similar increases in water intake between TRPV1−/− and WT mice (1.23±0.05 vs 1.01±0.06 mL). The ingestion of water stimulated by sole access to 2% NaCl for 48 hrs was not different between TRPV1−/− and WT mice (0.67±0.07 vs 0.76±0.06 mL). Hypovolemia produced by the diuretic furosemide (2.5 mg, sc) stimulated similar increases in water intake between TRPV1−/− and WT mice (0.63±0.03 vs 0.79±0.04 mL). Isoproterenol (0.4 μg, sc) also produced similar increases in water intake between TRPV1−/− and WT mice (0.27±0.02 vs 0.31±0.03 mL). TRPV1−/− mice were confirmed by PCR and the lack of an irritant response to capsaicin. These findings suggest that TRPV1 receptors are not necessary for osmotically‐driven thirst and may not be candidate ion channels that permit the brain to detect changes in systemic sodium concentration.