title: Corticotropin-releasing hormone receptor 1 coexists with endothelin-1 and modulates its mRNA expression and release in rat paraventricular nucleus during hypoxia.
abstract: To determine whether corticotropin-releasing hormone receptor 1 (CRHR1) coexists with endothelin-1 (ET-1) in rat paraventricular nucleus (PVN), ET-1 expression and its regulation by CRH and CRHR1 under hypoxia, rats were exposed to simulated continuous hypoxia at 5 km altitude (CH5km, equal to 10.8% O(2)) in a hypobaric chamber for 1, 2, 5, 10, 15 or 25 days. ET-1, CRH, and its mRNA were measured using radioimmunoassay (RIA), immunohistochemistry, and in situ hybridization. The coexistence of ET-1 and CRHR1 was identified by confocal immunofluorescence. The results showed that CH5km caused a significant decrease of ET-1 level in PVN at 5 days, but decreased CRH on days 1 and 2 while it increased on days 5 and 10. CH5km induced ET-1 mRNA upregulation and ET-1 decrease at 5 days, the effects were completely reversed by treatment with five-daily-injections of a CRHR1 antagonist (butyl-[2,5-dimethyl-7-(2,4,6-trimethylphenyl)-7H-pyrrolo[2,3-d] pyrimidin-4-yl]-ethylamine: CP-154,526). Also, this treatment significantly reversed the CH5km-induced increase in CRH and CRHmRNA in PVN at 5 days. Moreover we found that the changes in expression of ET-1 and CRHR1 induced by CH5km were co-localized in parvocellular PVN cells. In conclusion, CRHR1 coexists with ET-1 in parvocellular PVN, continuous hypoxia stimulates ET-1 and ET-1mRNA as well as CRH and CRHmRNA, and CRHR1 evidently modulates ET-1 release and ET-1mRNA activation caused by continuous hypoxia.
authors.affiliation: Division of Neurobiology and Physiology, College of Life Sciences, Zhejiang University School of Medicine, Zijingang Campus, Hangzhou, China.
authors.forename: J-J
authors.initials: JJ
authors.lastname: He
authors.forename: X-Q
authors.initials: XQ
authors.lastname: Chen
authors.forename: L
authors.initials: L
authors.lastname: Wang
authors.forename: J-F
authors.initials: JF
authors.lastname: Xu
authors.forename: J-Z
authors.initials: JZ
authors.lastname: Du
mesh_terms: D000818:Animals; D003345:Corticosterone / Q000097:blood; D019332:Endothelin-1 / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology*; D000860:Hypoxia / Q000188:drug therapy / Q000473:pathology*; D008297:Male; D010286:Paraventricular Hypothalamic Nucleus / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D011743:Pyrimidines / Q000627:therapeutic use; D011758:Pyrroles / Q000627:therapeutic use; D012333:RNA, Messenger / Q000378:metabolism; D011863:Radioimmunoassay / Q000379:methods; D051381:Rats; D017207:Rats, Sprague-Dawley; D018019:Receptors, Corticotropin-Releasing Hormone / Q000235:genetics / Q000378:metabolism*; D013997:Time Factors; D000099052:CRF Receptor, Type 1
chemical_list: C101628:CP 154526; D019332:Endothelin-1; D011743:Pyrimidines; D011758:Pyrroles; D012333:RNA, Messenger; D018019:Receptors, Corticotropin-Releasing Hormone; D000099052:CRF Receptor, Type 1; D003345:Corticosterone