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Mechanism of diminished contractile response to catecholamines during acidosis.

Abstract
To examine mechanisms of diminished contractile response to catecholamines during acidosis, we studied contractile properties, beta-adrenergic receptor properties, and intracellular pH of intact, cultured myocardial cells from chick embryo ventricle at pH 7.4 and 6.8. Contractile response was measured with an optical-video system. On changing the superfusing buffer from pH 7.4 to 6.8 there was a decline in contractile amplitude to 80% of control by 20 min. Fluorimetrically determined intracellular pH declined over a similar time course from 7.11 +/- 0.05 to 6.96 +/- 0.07 (P less than 0.05). After 45 min at pH 6.8 the contractile response to 1 microM isoproterenol was less than half of the response at pH 7.4. Antagonist and agonist ligand-binding properties of the beta-adrenergic receptor were determined in the intact cells under conditions identical to those for the contractility studies. With the use of the hydrophilic antagonist [3H]CGP-12177 that selectively labels cell-surface receptors, agonist competition studies demonstrated that acidosis had no significant effect on antagonist or agonist affinity but decreased beta-receptor number from 21 +/- 3 to 11 +/- 3 fmol/mg protein (P less than 0.02). It is probable that a decline in the number of beta-receptors on the cell surface contributes to contractile hyporesponsiveness to catecholamines during acidosis.
AuthorsJ D Marsh, T I Margolis, D Kim
JournalThe American journal of physiology (Am J Physiol) Vol. 254 Issue 1 Pt 2 Pg. H20-7 (Jan 1988) ISSN: 0002-9513 [Print] United States
PMID2827525 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)
Chemical References
  • Catecholamines
  • Propanolamines
  • Receptors, Adrenergic, beta
  • Isoproterenol
  • CGP 12177
Topics
  • Acidosis (physiopathology)
  • Animals
  • Catecholamines (pharmacology)
  • Cells, Cultured
  • Chick Embryo
  • Hydrogen-Ion Concentration
  • Isoproterenol (pharmacology)
  • Myocardial Contraction (drug effects)
  • Myocardium (metabolism)
  • Propanolamines (pharmacology)
  • Receptors, Adrenergic, beta (metabolism)

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