Sellinger-Barnette M, Weiss B
Mol Pharmacol. 1982 Jan;21(1):86-91.
A highly purified preparation of calmodulin activated a calmodulin-deficient phosphodiesterase by more than 10-fold. This activation of phosphodiesterase by calmodulin was completely inhibited by two opioid peptides, beta-endorphin and dynorphin, at concentrations that had no appreciable effect on the basal phosphodiesterase activity. By contrast, similar concentrations of other structurally related peptides, including alpha-endorphin, (des-Tyr1)-gamma-endorphin, Leu-enkephalin, and Met-enkephalin, failed to block calmodulin's activation of phosphodiesterase. The inhibition by beta-endorphin of calmodulin's action was not reversed by calcium or by the opiate antagonist naloxone but was overcome by increasing the concentration of calmodulin. Equilibrium dialysis studies showed that 125I-labeled beta-endorphin bound directly to calmodulin in a saturable, calcium-dependent manner with a dissociation constant of approximately 4.6 microM. There was substantially less binding of beta-endorphin to troponin-C and little or no calcium-dependent binding of beta-endorphin to bovine serum albumin, lactalbumin, or histone. This interaction of beta-endorphin with calmodulin was similar in several respects to the interaction of certain antipsychotic drugs to calmodulin and may explain certain of the peptide's biochemical effects.
一种高度纯化的钙调蛋白制剂可使缺乏钙调蛋白的磷酸二酯酶激活10倍以上。钙调蛋白对磷酸二酯酶的这种激活作用被两种阿片肽——β-内啡肽和强啡肽完全抑制，其浓度对基础磷酸二酯酶活性无明显影响。相比之下，其他结构相关肽，包括α-内啡肽、（去酪氨酸1）-γ-内啡肽、亮氨酸脑啡肽和甲硫氨酸脑啡肽，在类似浓度下未能阻断钙调蛋白对磷酸二酯酶的激活作用。β-内啡肽对钙调蛋白作用的抑制作用不能被钙或阿片拮抗剂纳洛酮逆转，但可通过增加钙调蛋白的浓度来克服。平衡透析研究表明，125I标记的β-内啡肽以饱和、钙依赖的方式直接与钙调蛋白结合，解离常数约为4.6微摩尔。β-内啡肽与肌钙蛋白-C的结合明显较少，与牛血清白蛋白、乳白蛋白或组蛋白几乎没有或没有钙依赖的结合。β-内啡肽与钙调蛋白的这种相互作用在几个方面与某些抗精神病药物与钙调蛋白的相互作用相似，这可能解释了该肽的某些生化作用。
