Original ArticleFunctional ETA-ETB Receptor Cross-talk in Basilar Artery In Situ From ETB Receptor Deficient RatsYoon, SeongHun PhD; Gariepy, Cheryl E. MD; Yanagisawa, Masashi MD; Zuccarello, Mario MD; Rapoport, Robert M. PhDAuthor Information *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. Reprints: Robert M. Rapoport, PhD, Department of Pharmacology and Cell Biophysics, University of Cincinnati College of Medicine, PO Box 670575, Cincinnati, OH 45267-0575 (e-mail: [email protected]). Drs. Yoon and Rapaport conducted research contained in this article at Research Service, Veterans Affairs Medical Center, Department of Pharmacology and Cell Biophysics, University of Cincinnati College of Medicine, Cincinnati, OH. Drs. Gariepy and Yanagisawa conducted research contained in this article at Howard Hughes Medical Institute and Department of Molecular Genetics, University of Texas Southwestern Medical School, Dallas, TX. Dr. Zuccarello conducted research contained in this article at Surgical Service, Veterans Affairs Medical Center, Department of Neurosurgery, the Neuroscience Institute, University of Cincinnati College of Medicine, Cincinnati, OH. Supported by grants from the Office of Research and Development, Medical Research Service, Department of Veterans Affairs and the Mayfield Educational Fund, Department of Neurosurgery, University of Cincinnati, Cincinnati, Ohio (R.M.R. and M.Z.) and the World Premier International Research Center Initiative from MEXT, Japan (M.Y.). M. Yanagisawa is a former investigator of the Howard Hughes Medical Institute. The authors report no conflicts of interest. Conception/design: R. M. Rapoport and M. Zuccarello; acquisition: S. Yoon; analysis: R. M. Rapoport; interpretation: C. E. Gariepy, R. M. Rapoport, and M. Yanagisawa; drafting/revising: all. All authors agree to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. Received August 07, 2015 Accepted October 06, 2015 Journal of Cardiovascular Pharmacology: March 2016 - Volume 67 - Issue 3 - p 212-217 doi: 10.1097/FJC.0000000000000335 Buy Metrics Abstract The role of endothelin (ET)A-ETB receptor cross-talk in limiting the ETA receptor antagonist inhibition of ET-1 constriction is revealed by the partial or complete dependency of the ETA receptor antagonist inhibition on functional removal of the ETB receptor. Although functional removal of the ETB receptor is generally accomplished with ETB receptor antagonist, a novel approach using rats containing a naturally occurring deletion mutation in the ETB receptor [rescued “spotting lethal” (sl) rats; ETBsl/sl] demonstrated increased ETA receptor antagonist inhibition of ET-1 constriction in vena cava. We investigated whether this deletion mutation was also sufficient to remove the ETB receptor dependency of the ETA receptor antagonist inhibition of ET-1 constriction in the basilar artery. Consistent with previous reports, ET-1 plasma levels were elevated in ETBsl/sl as compared with ETB+/+ rats. ETB receptor antagonist failed to relax the ET-1 constricted basilar artery from ETB+/+ and ETBsl/sl rats. Relaxation to combined ETA and ETB receptor antagonist was greater than relaxation to ETA receptor antagonist in the basilar artery from ETB+/+ and, unexpectedly, ETBsl/sl rats. These findings confirm the presence of ETA-ETB receptor cross-talk in the basilar artery. We speculate that mutant ETB receptor expression produced by alternative splicing may be sufficient to allow cross-talk. Copyright © 2016 Wolters Kluwer Health, Inc. All rights reserved.