Various mechanisms have been proposed for β-adrenergically mediated relaxation of smooth muscle. All theories suggest the involvement of cyclic AMP as a second messenger: β-agonists stimulate adenylate cyclase which converts ATP to cyclic AMP1 and protein kinase, activated by cyclic AMP, is then thought to catalyse a protein phosphorylation that leads to a reduction in free Ca2+, thus effecting relaxation1. How this last step is accomplished is much debated, but the following possibilities are currently considered as the mechanisms responsible for cyclic AMP-induced reduction of cytoplasmic Ca2+: activation of a Ca2+-ATPase in the plasma and/or sarcoplasmic reticulum membranes which lowers cytoplasmic [Ca2+] in a direct manner or stimulation of (Na+–K+)ATPase in the cell membrane which may indirectly effect Ca2+ extrusion2–8. Among the hypotheses suggested, those of Ca2+ sequestration by the sarcoplasmic reticulum and of Ca2+ extrusion across the cell membrane are consistent with each other if it is assumed that both processes are effected by a cyclic AMP-sensitive Ca2+-ATPase. However, quite a different mechanism is implied by involving the Na+–K2+ pump and Na+–Ca2+ exchange carrier. In this report, we present evidence that suggests intracellular Ca2+ sequestration is the mechanism involved.
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Mueller, E., van Breemen, C. Role of intracellular Ca2+ sequestration in β-adrenergic relaxation of a smooth muscle. Nature 281, 682–683 (1979). https://doi.org/10.1038/281682a0
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