Role of intracellular Ca²⁺ sequestration in β-adrenergic relaxation of a smooth muscle

Abstract

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⁺ extrusion^2–8. 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.