摘要
To determine whether the cyclic adenosine monophosphate (cAMP) mediated protein kinase signal transduction pathway is involved in the pyrogenic action of corticotropin releasing hormone (CRH) in rats.Methods Corticotropin releasing hormone, 2', 3 '-dideoxyadenosine (DDA) and adenosine-3', 5'(cyclic) monophosphorothionate, Rp-lsomer (Rp-cAMPS), were administered intracerebroventricularly (i.c.v.). The colonic temperature was measured using a thermistor, and the content of cAMP in the hypothalamus was determined by radioimmunoassay. Hypethalemic incubation was used to assess the effects of CRH on the content of cAMP in the hypothalamus in vitro.Results Microinjection (i.c.v.) of CRH (2.5 μg, 5.0 μg and 10 μg) caused increases in colonic temperature and the hypothalemus cAMP level in conscious rats. CRH increased hypothalemus cAMP level in vitro. The pyrogenic effects of CRH were abolished or markedly inhibited by prior injection (i. c. v. ) of an adenylate cyclase inhibitor, DDA (30 μg), or an inhibitor of cAMP-dependent protein kinase, Rp-cAMPS (15 μg).Conclusion cAMP mediates the pyrogenic action of centrally administered of CRH in rats, and protein kinase A may play an important role in the central CRH-induced fever. The cAMP-dependent protein kinase signal transduction pathway may be involved in the central mechanisms of the pyrogenic action of CRH in rats.
目的 观察cAMP依赖性蛋白激酶信号传导通路在大鼠CRH性发热机制中的作用。方法 第三脑室注射促肾上腺皮质激素释放激素 (CRH) ,腺苷酸环化酶抑制剂DDA或cAMP依赖性蛋白激酶抑制剂Rp cAMPS ,测定大鼠结肠温度。用放射免疫分析法测定下丘脑cAMP含量 ,并用离体实验观察CRH对下丘脑cAMP含量的影响。结果 第三脑室微量注射CRH(2 5 μg ,5 0 μg ,10 μg)引起大鼠结肠温度和下丘脑cAMP水平明显升高 ,下丘脑cAMP水平与大鼠 2小时发热反应指数之间存在明显的正相关 (r=0 994 ,P <0 0 1)。离体实验同样观察到CRH可引起下丘脑cAMP水平明显升高。事先向第三脑室微量注射腺苷酸环化酶抑制剂DDA 30 μg或cAMP依赖性蛋白激酶抑制剂Rp cAMPs 15 μg均显著抑制中枢注射CRH引起的发热反应。结论 这些结果证明 ,cAMP参与了大鼠CRH性发热的中枢机制 ,cAMP依赖性蛋白激酶可能在CRH性发热机制中发挥重要作用 ,cAMP依赖性蛋白激酶信号传导通路可能介导中枢注射CRH对大鼠的致热作用。
基金
ThisworkwassupportedbytheNationalNaturalScienceFoundationofChina (No 3970 0 0 5 5 )
