Fishman B E, Gianutsos G
Section of Pharmacology and Toxicology, University of Connecticut, Storrs 06268.
Life Sci. 1987 Oct 5;41(14):1703-9. doi: 10.1016/0024-3205(87)90597-2.
A number of different depressant and convulsant agents have been shown to alter accumulation of cerebellar cyclic GMP. Since the different hexachlorocyclohexane (HCH) isomers elicit different pharmacological responses in mammals, we examined their effects on the accumulation of cerebellar cyclic GMP. Mice received one of the HCH isomers and were sacrificed for determination of cyclic GMP concentrations one hour later. Gamma-HCH increased cyclic GMP while alpha and delta-HCH decreased it. In addition, alpha and delta-HCH prevented the increase in cyclic GMP due to the gamma isomer. Picrotoxin increased cyclic GMP in a manner similar to that of gamma-HCH while strychnine produced only a small increase. All three HCH isomers inhibited the binding of 3H-TBOB (a ligand for the GABA-A-receptor linked chloride channel) in mouse cerebellum. It is concluded that the different HCH isomers can have different effects on cerebellar cyclic GMP accumulation and that these effects may be mediated through actions at the GABA-A receptor linked chloride channel.
已证实多种不同的抑制剂和惊厥剂可改变小脑环磷酸鸟苷（cGMP）的蓄积。由于不同的六氯环己烷（HCH）异构体在哺乳动物中引发不同的药理反应，我们研究了它们对小脑cGMP蓄积的影响。给小鼠施用一种HCH异构体，1小时后处死小鼠以测定cGMP浓度。γ-六氯环己烷可增加cGMP，而α-和δ-六氯环己烷则使其降低。此外，α-和δ-六氯环己烷可抑制因γ-异构体导致的cGMP增加。印防己毒素增加cGMP的方式与γ-六氯环己烷相似，而士的宁仅产生少量增加。所有三种HCH异构体均抑制3H-TBOB（一种GABA-A受体连接氯离子通道的配体）与小鼠小脑的结合。得出的结论是，不同的HCH异构体对小脑cGMP蓄积可产生不同影响，且这些影响可能通过作用于GABA-A受体连接氯离子通道来介导。
