HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

Transcriptional regulation of left ventricular beta-adrenergic receptors during chronic hypoxia.

Abstract
beta-Adrenergic receptor downregulation is the end result of cellular adaptation to prolonged agonist exposure. The factors mediating receptor downregulation include receptor phosphorylation, receptor movement from the plasma membrane to intracellular sites, and alterations in nascent receptor synthesis. We have previously demonstrated a downregulation of the left ventricular beta-receptor during chronic hypoxia in vivo. To determine the mechanism of this downregulation, we produced chronic hypoxia in seven newborn lambs by creating right ventricular outflow obstruction and an atrial septal defect. Oxygen saturation was reduced to 65-74% for 2 weeks. Six lambs served as normoxic controls. Sarcolemmal membrane and cytosolic fractions were prepared from left ventricular free wall samples. beta-Receptor density in each fraction was determined with the radioligand [125I]iodocyanopindolol. Steady-state levels of beta-receptor mRNA were determined by Northern blot analysis using a beta 1-adrenergic receptor cDNA probe. During chronic hypoxia, left ventricular membrane beta-adrenergic receptor density decreased by 55% (153 +/- 28 fmol/mg for hypoxic lambs versus 342 +/- 79 fmol/mg for control lambs, p < 0.05). There was no corresponding increase in beta-receptor density in the cytosolic fraction (23 +/- 3 fmol/mg for hypoxic lambs versus 33 +/- 9 fmol/mg for control lambs, p = NS), nor was there a significant change in the ratio of beta 1-receptor/beta 2-receptor subtypes as assessed by radioligand binding (beta 1 subtype, 84.1 +/- 10.1% for hypoxic lambs versus 93.2 +/- 8.8% for control lambs; p = NS).(ABSTRACT TRUNCATED AT 250 WORDS)
AuthorsD Bernstein, R Doshi, S Huang, E Strandness, J R Jasper
JournalCirculation research (Circ Res) Vol. 71 Issue 6 Pg. 1465-71 (Dec 1992) ISSN: 0009-7330 [Print] United States
PMID1330359 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
Chemical References
  • RNA, Messenger
  • Receptors, Adrenergic, beta
Topics
  • Animals
  • Autoradiography
  • Blotting, Northern
  • Chronic Disease
  • Cyanosis (physiopathology)
  • Heart Defects, Congenital (physiopathology)
  • Hypoxia (genetics, physiopathology)
  • RNA, Messenger (genetics)
  • Receptors, Adrenergic, beta (classification, genetics, physiology)
  • Sheep
  • Transcription, Genetic

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: