Gnegy M E
Fed Proc. 1982 May;41(7):2273-7.
Increasing evidence suggests a relationship between dopaminergic activity in the striatum and the content of calmodulin (CaM), an endogenous Ca2+-binding protein. The content of CaM in striatal membranes is increased by treatments that produce supersensitivity in striatal membranes is increased by treatments that produce supersensitivity of striatal dopaminergic receptors such as chronic neuroleptic treatment or injection of 6-hydroxydopamine. Concomitant with the increase in CaM is a greater sensitivity of adenylate cyclase to dopamine and an increase in Ca2+-sensitive phosphorylation in the striatal membranes. Procedures that result in dopaminergic subsensitivity, such as amphetamine treatment, increase the cytosolic content of CaM that can subsequently activate Ca2+ and CaM-dependent phosphodiesterase activity. In vitro studies have demonstrated that CaM and Ca2+ can stimulate basal adenylate cyclase activity in a striatal particulate fraction as well as increase the sensitivity of the enzyme to dopamine. Ca2+ and CaM most likely affect the dopamine-sensitive adenylate cyclase by interacting with guanyl nucleotides, which are required for dopamine sensitivity. It is concluded that a change in CaM concentration and/or location occurs during conditions of altered dopaminergic sensitivity in the striatum. These changes in CaM coupled with potential alterations in the Ca2+ concentration could modulate the sensitivity of the dopamine system and many CaM-dependent enzymes.
越来越多的证据表明，纹状体中的多巴胺能活性与钙调蛋白（CaM，一种内源性Ca2+结合蛋白）的含量之间存在关联。纹状体膜中CaM的含量会因一些处理而增加，这些处理会使纹状体膜产生超敏反应，例如长期使用抗精神病药物治疗或注射6-羟基多巴胺，这些处理会使纹状体多巴胺能受体产生超敏反应。与CaM增加相伴的是腺苷酸环化酶对多巴胺的敏感性增强以及纹状体膜中Ca2+敏感的磷酸化增加。导致多巴胺能低敏的程序，如安非他明治疗，会增加CaM的胞质含量，随后可激活Ca2+和CaM依赖性磷酸二酯酶活性。体外研究表明，CaM和Ca2+可刺激纹状体微粒体部分的基础腺苷酸环化酶活性，并增加该酶对多巴胺的敏感性。Ca2+和CaM很可能通过与鸟苷酸相互作用来影响多巴胺敏感的腺苷酸环化酶，而鸟苷酸是多巴胺敏感性所必需的。得出的结论是，在纹状体多巴胺能敏感性改变的情况下，CaM浓度和/或位置会发生变化。这些CaM的变化以及Ca2+浓度的潜在改变可能会调节多巴胺系统和许多CaM依赖性酶的敏感性。
