title: Intestinal Na+ loss and volume depletion in JAK3-deficient mice.
abstract: OBJECTIVE
  The Janus kinase 3 JAK3 participates in the signaling of immune cells. Lack of JAK3 triggers inflammatory bowel disease, which in turn has been shown to affect intestinal activity of the epithelial Na(+) channel ENaC and thus colonic sodium absorption. At least in theory, inflammatory bowel disease in JAK3-deficient mice could lead to intestinal salt loss compromizing extracellular volume maintenance and blood pressure regulation. The present study thus explored whether JAK3 deficiency impacts on colonic ENaC activity, fecal Na(+) exretion, blood pressure and extracellular fluid volume regulation.
  
  
  METHODS
  Experiments were performed in gene-targeted mice lacking functional JAK3 (jak3(-/-)) and in wild type mice (jak3(+/+)). Colonic ENaC activity was estimated from amiloride-sensitive current in Ussing chamber experiments, fecal, serum and urinary Na(+) concentration by flame photometry, blood pressure by the tail cuff method and serum aldosterone levels by immunoassay.
  
  
  RESULTS
  The amiloride (50 µM)-induced deflection of the transepithelial potential difference was significantly lower and fecal Na(+) excretion significantly higher in jak3(-/-) mice than in jak3(+/+) mice. Moreover, systolic arterial blood pressure was significantly lower and serum aldosterone concentration significantly higher in jak3(-/-) mice than in jak3(+/+) mice. Both, absolute and fractional renal Na(+) excretion were significantly lower in jak3(-/-) mice than in jak3(+/+) mice.
  
  
  CONCLUSIONS
  JAK3 deficiency leads to impairment of colonic ENaC activity with intestinal Na(+) loss, decrease of blood pressure, increased aldosterone release and subsequent stimulation of renal tubular Na(+) reabsorption.
authors.affiliation: Department of Physiology, University of Tübingen, Germany.
authors.forename: Anja T
authors.initials: AT
authors.lastname: Umbach
authors.forename: Dong
authors.initials: D
authors.lastname: Luo
authors.forename: Shefalee K
authors.initials: SK
authors.lastname: Bhavsar
authors.forename: Zohreh
authors.initials: Z
authors.lastname: Hosseinzadeh
authors.forename: Florian
authors.initials: F
authors.lastname: Lang
mesh_terms: D000818:Animals; D003106:Colon / Q000378:metabolism*; D053503:Epithelial Sodium Channels / Q000378:metabolism*; D005260:Female; D005769:Gastrointestinal Motility / Q000502:physiology*; D020896:Hypovolemia / Q000175:diagnosis / Q000378:metabolism*; D053616:Janus Kinase 3 / Q000172:deficiency*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D012964:Sodium / Q000378:metabolism*
chemical_list: D053503:Epithelial Sodium Channels; D012964:Sodium; C507935:Jak3 protein, mouse; D053616:Janus Kinase 3