福斯高林对大鼠纹状体酪氨酸羟化酶的刺激是否依赖于腺苷酸环化酶的激活？

Is forskolin stimulation of rat striatal tyrosine hydroxylase dependent on adenylate cyclase activation?

作者信息

Onali P, Olianas M C

机构信息

Department of Neurosciences, University of Cagliari, Italy.

出版信息

Neurosci Lett. 1992 Oct 12;145(2):161-4. doi: 10.1016/0304-3940(92)90011-u.

DOI:10.1016/0304-3940(92)90011-u

PMID:1361222

Abstract

Because some responses to forskolin are adenosine 3',5'-cyclic phosphate (cyclic AMP) independent, we investigated the involvement of adenylate cyclase in the stimulatory effect of forskolin on synaptosomal tyrosine hydroxylase (TH) activity of rat striatum. The forskolin analogue, 1,9-dideoxyforskolin, which mimics the cyclic AMP-independent effects of forskolin, was a very weak activator of both striatal adenylate cyclase and tyrosine hydroxylase activities, whereas forskolin stimulated the two enzymes effectively and with similar potencies. Moreover, exposure of synaptosomes to the specific cyclic AMP antagonist Rp-adenosine 3',5'-cyclic phosphorothioate reduced basal TH activity and counteracted the stimulatory effect on the enzyme activity by submaximal concentrations of forskolin. These results provide circumstantial evidence that in striatal dopaminergic nerve terminals a presynaptic adenylate cyclase mediates the stimulation of TH activity by forskolin.

摘要

由于对福司可林的一些反应不依赖于腺苷3',5'-环磷酸（环磷酸腺苷），我们研究了腺苷酸环化酶在福司可林对大鼠纹状体突触体酪氨酸羟化酶（TH）活性的刺激作用中的参与情况。福司可林类似物1,9-二脱氧福司可林可模拟福司可林不依赖环磷酸腺苷的效应，它对纹状体腺苷酸环化酶和酪氨酸羟化酶活性的激活作用非常微弱，而福司可林能有效刺激这两种酶，且效力相似。此外，将突触体暴露于特异性环磷酸腺苷拮抗剂Rp-腺苷3',5'-环硫代磷酸酯会降低基础TH活性，并抵消亚最大浓度福司可林对酶活性的刺激作用。这些结果间接证明，在纹状体多巴胺能神经末梢中，一种突触前腺苷酸环化酶介导了福司可林对TH活性的刺激作用。