title: Suppression of TRPV4 channels ameliorates anti-dipsogenic effects under hypoxia in the subfornical organ of rats.
abstract: The phenomenon of water intake reduction during the 1(st) day of hypobaric hypoxia has been known for a long time. However, the reason for the same is yet unknown. The transient receptor potential vanilloid (TRPV) channels, including TRPV1 and TRPV4, are located in the subfornical organ (SFO). These are calcium permeable cationic channels gated by various stimuli such as cell swelling, low pH, and high temperature, and participate in anti-dipsogenic effects when activated. We aimed to explore the drinking behavior of rats and the mechanism of TRPVs under hypoxia. Chemical TRPV4 inhibitors (HC-067047 and Gadolinium) or TRPV4 knockout, but not TRPV1 inhibitor SB-705498, could restore the water intake under hypoxia. Hypoxia-mediated direct activation of TRPV4 may be the reason of anti-dipsogenic effects because the serum sodium, pH, and intracranial temperature are unaltered. Interestingly, we found that hypoxia immediately increased the intracellular Ca(2+) concentration ([Ca(2+)]i) in HEK293-TRPV4 cells and primary neurons from SFO region, but not in the HEK293-TRPV1 cells. Moreover, hypoxia-induced [Ca(2+)]i increase depended on the indispensable hemeoxygenase-2 (HO-2) and TRPV4. HO-2 and TRPV4 were also confirmed to form a complex in SFO neurons. These results demonstrated that SFO cells sense hypoxia and activate via the HO-2/TRPV4 multiple channels, which are associated with anti-dipsogenic effects.
authors.affiliation: Department of Pathophysiology and High Altitude Pathology, College of High Altitude Military Medicine, Third Military Medical University, 30 Gaotanyan, Shapingba, Chongqing, 400038,China.|Key Laboratory of High Altitude Medicine (Third Military Medical University), Ministry of Education, Chongqing, China.|Key Laboratory of High Altitude Medicine, PLA, Chongqing, China.
authors.forename: Fan
authors.initials: F
authors.lastname: Yang
authors.affiliation: Department of pharmacy, Xinqiao Hospital &The Second Affiliated Hospital, The Third Military Medical University, Chongqing, China.
authors.forename: Li
authors.initials: L
authors.lastname: Zhou
authors.affiliation: Department of Pathophysiology and High Altitude Pathology, College of High Altitude Military Medicine, Third Military Medical University, 30 Gaotanyan, Shapingba, Chongqing, 400038,China.|Key Laboratory of High Altitude Medicine (Third Military Medical University), Ministry of Education, Chongqing, China.|Key Laboratory of High Altitude Medicine, PLA, Chongqing, China.
authors.forename: Dong
authors.initials: D
authors.lastname: Wang
authors.affiliation: Department of nuclear medicine, Kunming General Hospital of Chengdu Military Area, China.
authors.forename: Li-Li
authors.initials: LL
authors.lastname: Yang
authors.affiliation: Department of nuclear medicine, Kunming General Hospital of Chengdu Military Area, China.
authors.forename: Guo-Rong
authors.initials: GR
authors.lastname: Yuan
authors.affiliation: Department of Pathophysiology and High Altitude Pathology, College of High Altitude Military Medicine, Third Military Medical University, 30 Gaotanyan, Shapingba, Chongqing, 400038,China.|Key Laboratory of High Altitude Medicine (Third Military Medical University), Ministry of Education, Chongqing, China.|Key Laboratory of High Altitude Medicine, PLA, Chongqing, China.
authors.forename: Qing-Yuan
authors.initials: QY
authors.lastname: Huang
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D002460:Cell Line; D004326:Drinking / Q000187:drug effects; D005682:Gadolinium / Q000494:pharmacology; D057809:HEK293 Cells; D006419:Heme Oxygenase (Decyclizing) / Q000378:metabolism; D006801:Humans; D006863:Hydrogen-Ion Concentration; D000860:Hypoxia / Q000378:metabolism*; D008297:Male; D009025:Morpholines / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D011758:Pyrroles / Q000494:pharmacology; D011759:Pyrrolidines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012964:Sodium / Q000097:blood; D013356:Subfornical Organ / Q000187:drug effects / Q000378:metabolism*; D050916:TRPV Cation Channels / Q000378:metabolism*; D013696:Temperature; D014508:Urea / Q000031:analogs & derivatives / Q000494:pharmacology
chemical_list: C573308:HC-067047; D009025:Morpholines; D011758:Pyrroles; D011759:Pyrrolidines; C512301:SB 705498; D050916:TRPV Cation Channels; C486577:Trpv4 protein, rat; D014508:Urea; D012964:Sodium; D005682:Gadolinium; D006419:Heme Oxygenase (Decyclizing); D002118:Calcium