title: Functional ET(A)-ET(B) Receptor Cross-talk in Basilar Artery In Situ From ET(B) Receptor Deficient Rats.
abstract: The role of endothelin (ET)(A)-ET(B) receptor cross-talk in limiting the ET(A) receptor antagonist inhibition of ET-1 constriction is revealed by the partial or complete dependency of the ET(A) receptor antagonist inhibition on functional removal of the ET(B) receptor. Although functional removal of the ET(B) receptor is generally accomplished with ET(B) receptor antagonist, a novel approach using rats containing a naturally occurring deletion mutation in the ET(B) receptor [rescued "spotting lethal" (sl) rats; ET(B)(sl/sl)] demonstrated increased ET(A) receptor antagonist inhibition of ET-1 constriction in vena cava. We investigated whether this deletion mutation was also sufficient to remove the ET(B) receptor dependency of the ET(A) receptor antagonist inhibition of ET-1 constriction in the basilar artery. Consistent with previous reports, ET-1 plasma levels were elevated in ET(B)(sl/sl) as compared with ET(B)(+/+) rats. ET(B) receptor antagonist failed to relax the ET-1 constricted basilar artery from ET(B)(+/+) and ET(B)(sl/sl) rats. Relaxation to combined ET(A) and ET(B) receptor antagonist was greater than relaxation to ET(A) receptor antagonist in the basilar artery from ET(B)(+/+) and, unexpectedly, ET(B)(sl/sl) rats. These findings confirm the presence of ET(A)-ET(B) receptor cross-talk in the basilar artery. We speculate that mutant ET(B) receptor expression produced by alternative splicing may be sufficient to allow cross-talk.
authors.affiliation: *Department of Cell Biology and Molecular Medicine, New Jersey Medical School, Rutgers University, Newark, NJ; †The Department of Pediatric Gastroenterology, The Ohio State University and Nationwide Children's Hospital Columbus, OH; ‡International Institute for Integrative Sleep Medicine (WPI-IIIS), University of Tsukuba, Tsukuba, Japan; §Department of Neurosurgery, The Neuroscience Institute, University of Cincinnati College of Medicine, Cincinnati, OH; and ‖Department of Pharmacology and Cell Biophysics, University of Cincinnati College of Medicine, Cincinnati, OH.
authors.forename: SeongHun
authors.initials: S
authors.lastname: Yoon
authors.forename: Cheryl E
authors.initials: CE
authors.lastname: Gariepy
authors.forename: Masashi
authors.initials: M
authors.lastname: Yanagisawa
authors.forename: Mario
authors.initials: M
authors.lastname: Zuccarello
authors.forename: Robert M
authors.initials: RM
authors.lastname: Rapoport
mesh_terms: D000818:Animals; D001488:Basilar Artery / Q000187:drug effects / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D065130:Endothelin A Receptor Antagonists / Q000494:pharmacology; D065131:Endothelin B Receptor Antagonists / Q000494:pharmacology; D019332:Endothelin-1 / Q000097:blood; D005838:Genotype; D010641:Phenotype; D011922:Rats, Mutant Strains; D017207:Rats, Sprague-Dawley; D020239:Receptor Cross-Talk; D044022:Receptor, Endothelin A / Q000187:drug effects / Q000378:metabolism*; D044023:Receptor, Endothelin B / Q000172:deficiency* / Q000235:genetics; D017384:Sequence Deletion; D015398:Signal Transduction; D014661:Vasoconstriction / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects
chemical_list: D065130:Endothelin A Receptor Antagonists; D065131:Endothelin B Receptor Antagonists; D019332:Endothelin-1; D044022:Receptor, Endothelin A; D044023:Receptor, Endothelin B