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Hormone-induced Desensitisation of Hormonal Control of Cyclic AMP Levels in Human Diploid Fibroblasts

Abstract

THE elevation of cyclic AMP levels in response to hormonal stimulation in many cells and tissues is transient1–5. In the absence of an inhibitor of phosphodiesterase actiiity, much of the newly synthesised nucleotide is rapidly degraded to AMP. When an inhibitor of phosphodiesterase is added to cells or tissues in vitro the level of cyclic AMP usually rises rapidly to a maximum following hormonal stimulation of adenyl cyclase. This suggests that the activation of adenyl cyclase is itself transient. Ho and Sutherland1 found that following stimulation of isolated rat adipocytes with adrenaline there was a refractory period during which the cells failed to respond (in terms of elevation of intracellular cyclic AMP) to further hormonal stimulation with either adrenaline, ACTH or glucagon. This is similar to the pharmacological phenomenon of tachyphylaxis and could provide a biochemical basis for the tachyphylaxis of β-receptors in isolated aortic smooth muscle6.

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FRANKLIN, T., FOSTER, S. Hormone-induced Desensitisation of Hormonal Control of Cyclic AMP Levels in Human Diploid Fibroblasts. Nature New Biology 246, 146–148 (1973). https://doi.org/10.1038/newbio246146a0

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