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Mechanism of diminished contractile response to catecholamines during acidosis

Journal Article · · American Journal of Physiology; (USA)
OSTI ID:7190433
; ;  [1]
  1. Brigham and Women's Hospital, Boston, MA (USA) Harvard Medical School, Boston, MA (USA)
To examined mechanisms of diminished contractile response to catecholamines during acidosis, the authors 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. 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 {plus minus} 0.05 to 6.96 {plus minus} 0.07. After 45 min at pH 6.8 the contractile response to 1 {mu}M 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 ({sup 3}H)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 {plus minus} 3 to 11 {plus minus} 3 fmol/mg protein. It is probably that a decline in the number of {beta}-receptors on the cell surface contributes to contractile hyporesponsiveness to catecholamines during acidosis.
OSTI ID:
7190433
Journal Information:
American Journal of Physiology; (USA), Journal Name: American Journal of Physiology; (USA) Vol. 254:1; ISSN 0002-9513; ISSN AJPHA
Country of Publication:
United States
Language:
English