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Colchicine potentiates β-adrenoreceptor-stimulated cyclic AMP in lymphoma cells by an action distal to the receptor

Abstract

THE cellular cytoskeleton, composed of microtubules and microfilaments, seems to regulate cell surface receptors for a number of membrane-active agents, including lectins1, immunoglobulins2 and polypeptide hormones3. Patching and capping of membrane receptors is controlled by the activity of microfilaments and microtubules, and, in addition, the cytoskeletal elements may be involved in stabilising the fluidity of the cell surface4,5. Colchicine, an inhibitor of microtubular assembly, and presumably, therefore, of microtubule-associated functions, has been used experimentally to study cellular events thought to be regulated by microtubules5, and clinically in the treatment of gout and other inflammatory disorders6. Evidence from several laboratories indicates that increases in cellular adenosine 3′,5′-monophosphate (cyclic AMP) alter the assembly of micro-tubules7–12. It has been suggested that colchicine augments hormone-stimulated cyclic AMP synthesis in target cells for some13,14, but not all15,18, hormones. To study this latter action of colchicine on a well-defined hormonal system, we have examined the augmentation by colchicine of β-adrenergic amine-stimulated cyclic AMP levels in S49 mouse lymphoma cells, a model system for studying the synthesis of cyclic AMP and the actions of β-adrenergic amines17,18. We report here that colchicine potentiates β-adrenergic-stimulated cyclic AMP accumulation in S49 cells and that this potentiation results from events occurring beyond the interaction of β-adrenergic agonists with β-adrenoreceptors.

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INSEL, P., KENNEDY, M. Colchicine potentiates β-adrenoreceptor-stimulated cyclic AMP in lymphoma cells by an action distal to the receptor. Nature 273, 471–473 (1978). https://doi.org/10.1038/273471a0

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