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Molecular Pharmacology, Vol 11, 485-491, Copyright © 1975 by the American Society for Pharmacology and Experimental Therapeutics

Desensitization of Beta Adrenergic Receptors in Human Fibroblasts in Tissue Culture

T. J. FRANKLIN 1, W. P. MORRIS 1, and P. A. TWOSE 1

1 Department of Biochemistry, Pharmaceuticals Division, Imperial Chemical Industries, Ltd., Alderley Park, Macclesfield, Cheshire, England

The ability of isoproterenol, epinephrine, norepinephrine, and salbutamol to desensitize the beta receptor-coupled cyclic 3',5'-AMP response of human diploid fibroblasts in tissue culture correlates well with their activity as beta stimulants. Partial desensitization of the cells results in a marked fall in the maximal cyclic AMP response to isoproterenol: fully desensitized cells are totally unresponsive to isoproterenol. Recovery of beta adrenergic sensitivity is a slow process and is delayed by extremely low concentrations of isoproterenol (picomolar). Recovery is also inhibited by concentrations of puromycin, cycloheximide, and actinomycin D that inhibit protein or RNA synthesis.

Submitted on February 5, 1975






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