促甲状腺激素释放激素（TRH）及其类似物（DN - 1417）：与戊巴比妥在大鼠大脑皮层切片耗氧量及环磷酸腺苷生成方面的相互作用

Thyrotropin-releasing hormone (TRH) and its analog (DN-1417): interaction with pentobarbital in oxygen consumption and cyclic AMP formation of rat cerebral cortex slices.

作者信息

Narumi S, Nagai Y, Saji Y, Nagawa Y

出版信息

Life Sci. 1984 May 28;34(22):2177-84. doi: 10.1016/0024-3205(84)90318-7.

Abstract

Effects of TRH or its analog DN-1417 (gamma-butyrolactone-gamma-carbonyl-L-histidyl-L- prolinamide ) and pentobarbital, alone or in combination, on oxygen consumption and cyclic AMP formation in rat cerebral cortex slices were investigated. The oxygen consumption of rat cerebral cortex slices as measured with a Warburg apparatus, increased linearly over time (0 to 60-min incubation at 37C). Addition of pentobarbital (1 to 7 x 10-4M) inhibited oxygen consumption, in a concentration-dependent manner, up to 45% of control. A concomitant application of DN-1417 (10-5M) or TRH (10-4M) and pentobarbital (5 x 10-4M) led to a partial recovery of the pentobarbital effect. The similar anti-pentobarbital effects were observed with the addition of carbachol (10-4M) or dibutyryl cyclic AMP (10-3M), but not norepinephrine (10-4M) or dopamine (10-4M). DN-1417, TRH, carbachol, norepinephrine or dopamine at 10-4M stimulated cyclic AMP formation in the cerebral cortex slices. Addition of pentobarbital (1 to 7 x 10-4M) inhibited the cyclic AMP formation, in a concentration-dependent manner. DN-1417, TRH or carbachol at 10-4M but not norepinephrine or dopamine at 10-4M significantly reversed the reduction of cyclic AMP formation induced by pentobarbital (5 x 10-4M). Atropine (10-4M) almost completely abolished DN-1417-, TRH- and carbachol-induced cyclic AMP formation in the presence and absence of pentobarbital.

摘要

研究了促甲状腺激素释放激素（TRH）或其类似物DN - 1417（γ-丁内酯-γ-羰基-L-组氨酰-L-脯氨酰胺）与戊巴比妥单独或联合使用对大鼠大脑皮层切片耗氧量和环磷酸腺苷（cAMP）生成的影响。用瓦氏呼吸仪测定，大鼠大脑皮层切片的耗氧量随时间呈线性增加（在37℃孵育0至60分钟）。添加戊巴比妥（1至7×10⁻⁴M）以浓度依赖方式抑制耗氧量，最高可达对照的45%。同时应用DN - 1417（10⁻⁵M）或TRH（10⁻⁴M）与戊巴比妥（5×10⁻⁴M）可使戊巴比妥的作用部分恢复。添加卡巴胆碱（10⁻⁴M）或二丁酰环磷酸腺苷（10⁻³M）时也观察到类似的抗戊巴比妥作用，但添加去甲肾上腺素（10⁻⁴M）或多巴胺（10⁻⁴M）时未观察到。10⁻⁴M的DN - 1417、TRH、卡巴胆碱、去甲肾上腺素或多巴胺可刺激大脑皮层切片中环磷酸腺苷的生成。添加戊巴比妥（1至7×10⁻⁴M）以浓度依赖方式抑制环磷酸腺苷的生成。10⁻⁴M的DN - 1417、TRH或卡巴胆碱可显著逆转戊巴比妥（5×10⁻⁴M）诱导的环磷酸腺苷生成减少，而10⁻⁴M的去甲肾上腺素或多巴胺则不能。在有和没有戊巴比妥存在的情况下，阿托品（10⁻⁴M）几乎完全消除了DN - 1417、TRH和卡巴胆碱诱导的环磷酸腺苷生成。