锂在体外和体内对脑内腺苷酸环化酶的作用是通过不同机制实现的。

The effects of lithium in vitro and ex vivo on adenylate cyclase in brain are exerted by distinct mechanisms.

作者信息

Mørk A, Geisler A

机构信息

Department of Pharmacology, University of Copenhagen, Denmark.

出版信息

Neuropharmacology. 1989 Mar;28(3):307-11. doi: 10.1016/0028-3908(89)90108-1.

DOI:10.1016/0028-3908(89)90108-1

PMID:2542834

Abstract

The effects of lithium on basal and forskolin-stimulated activity of adenylate cyclase in membrane preparations from cerebral cortex of the rat have been studied. Chronic treatment with lithium, yielding a level of lithium in serum of 0.71 +/- 0.18 mmol/l, reduced forskolin-stimulated activity in total homogenates but exerted no effect on the basal activity. Lithium in vitro, at 2 and 10 mM, did not influence the basal enzyme activity in membranes from either control or lithium-treated animals. The sensitivity of forskolin-stimulated adenylate cyclase to lithium in vitro was unaltered after chronic treatment and the in vitro and ex vivo effects of lithium on this parameter were additive. The inhibitory ex vivo effect of lithium was not antagonized by increasing concentrations of magnesium and the inhibitory effect of lithium ex vivo was still persistent after washing of the membranes. The present results indicate that lithium exerts its ex vivo effect on the activated cyclase, independently of the in vitro effect. Both effects may, however, contribute to the in vivo effect of lithium during chronic treatment.

摘要

研究了锂对大鼠大脑皮层膜制剂中腺苷酸环化酶基础活性和福斯高林刺激活性的影响。锂的长期治疗使血清锂水平达到0.71±0.18 mmol/l，降低了福斯高林刺激的总匀浆活性，但对基础活性没有影响。体外2 mM和10 mM的锂对对照组或锂处理组动物的膜中基础酶活性均无影响。长期治疗后，福斯高林刺激的腺苷酸环化酶对体外锂的敏感性未改变，锂对该参数的体外和体内效应具有加和性。增加镁的浓度并不能拮抗锂的体内抑制作用，且膜洗涤后锂的体内抑制作用仍然存在。目前的结果表明，锂对活化环化酶的体内作用独立于体外作用。然而，这两种作用都可能有助于锂在长期治疗期间的体内效应。