Mueller E, van Breemen C
Nature. 1979 Oct 25;281(5733):682-3. doi: 10.1038/281682a0.
Various mechanisms have been proposed for beta-adrenergically mediated relaxation of smooth muscle. All theories suggest the involvement of cyclic AMP as a second messenger: beta-agonists stimulate adenylate cyclase which converts ATP to cyclic AMP 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 relaxation. 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+ extrusion. 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+-K+ pump and Na+-Ca2+ exchange carrier. In this report, we present evidence that suggests intracellular Ca2+ sequestration is the mechanism involved.
对于β-肾上腺素能介导的平滑肌舒张，人们提出了多种机制。所有理论都表明环磷酸腺苷（cAMP）作为第二信使参与其中：β-激动剂刺激腺苷酸环化酶，该酶将三磷酸腺苷（ATP）转化为环磷酸腺苷，然后由环磷酸腺苷激活的蛋白激酶被认为催化蛋白质磷酸化，导致游离钙离子（Ca2+）减少，从而实现舒张。最后这一步是如何完成的存在很多争议，但目前认为以下几种可能性是环磷酸腺苷诱导细胞质钙离子减少的机制：激活质膜和/或肌浆网膜中的钙离子-ATP酶，以直接方式降低细胞质中的[Ca2+]，或刺激细胞膜中的（钠-钾）ATP酶，这可能间接影响钙离子的排出。在所提出的假设中，如果假定这两个过程均由环磷酸腺苷敏感的钙离子-ATP酶介导，那么肌浆网对钙离子的隔离和钙离子跨细胞膜的排出这两种假设是相互一致的。然而，涉及钠-钾泵和钠-钙交换载体则意味着一种截然不同的机制。在本报告中，我们提供的证据表明，细胞内钙离子的隔离是其中涉及的机制。
