Lugnier C
Laboratoire de pharmacologie cellulaire et moléculaire, CNRS URA 600, université Louis Pasteur de Strasbourg, Illkirch.
Arch Mal Coeur Vaiss. 1991 Jan;84 Spec No 1:25-34.
Calmodulin is a small protein (16.7 KDa) calcium receptor which plays a fundamental part in vasomotricity. When intracellular Ca2+ concentrations increase (from 0.1 to 10 M), calmodulin fixes four Ca2+, changes its conformation and interacts with its target proteins. In vascular smooth muscle it activates the kinase of the myosine light chain and interacts with caldesmone to allow phosphorylation of myosine and the actine-myosine interaction. These two processes lead to vascular smooth muscle contraction. Calmodulin also activates enzymes involved in the regulation of the cyclic nucleotides: adenylate cyclase which synthesises cyclic AMP and the calmodulin dependent phophodiesterase which preferentially hydrollyses cyclic GMP. Cyclic AMP and GMP contribute to the relaxation of smooth muscle by inhibiting, the kinase of the myosine light chain and stimulating the Ca2+ ATPase responsible for the extrusion of Ca2+. The contractile action of calmodulin is counterbalanced by the relaxing effects of cyclic AMP and GMP. In addition, caldomodulin participates in the control of vasomotricity by regulating the phosphorylation and dephosphorylation of proteins influencing intracellular Ca2+ concentrations and the activation of contractile proteins. Caldomodulin activates the enzyme responsible for the synthesis of nitric oxide in the endothelium (endothelium derived relaxing factor) and thereby participates in the endothelium dependent relaxation process.
钙调蛋白是一种小蛋白(16.7千道尔顿)钙受体,在血管舒缩中起重要作用。当细胞内钙离子浓度升高(从0.1微摩尔升至10微摩尔)时,钙调蛋白结合4个钙离子,改变其构象并与靶蛋白相互作用。在血管平滑肌中,它激活肌球蛋白轻链激酶并与钙调蛋白结合蛋白相互作用,使肌球蛋白磷酸化并促进肌动蛋白-肌球蛋白相互作用。这两个过程导致血管平滑肌收缩。钙调蛋白还激活参与环核苷酸调节的酶:合成环磷酸腺苷的腺苷酸环化酶和优先水解环磷酸鸟苷的钙调蛋白依赖性磷酸二酯酶。环磷酸腺苷和环磷酸鸟苷通过抑制肌球蛋白轻链激酶和刺激负责钙离子外排的钙离子ATP酶,促进平滑肌舒张。钙调蛋白的收缩作用被环磷酸腺苷和环磷酸鸟苷的舒张作用所抵消。此外,钙调蛋白通过调节影响细胞内钙离子浓度的蛋白质的磷酸化和去磷酸化以及收缩蛋白的激活,参与血管舒缩的控制。钙调蛋白激活内皮细胞中负责一氧化氮合成的酶(内皮源性舒张因子),从而参与内皮依赖性舒张过程。