Mardon K, Kassiou M, Donald A
Radiopharmaceutical Division R&D, Australian Nuclear Science and Technology Organisation, NSW.
Life Sci. 1999 Oct 29;65(23):PL 281-6. doi: 10.1016/s0024-3205(99)00521-4.
To study the effect of diabetes mellitus on the density of sigma receptors, in vitro binding experiments were conducted in whole brain homogenate membranes of 5-week and 10-week control rats and streptozotocin (STZ)-induced diabetic rats. sigma-1 Receptors were labelled with 3H-pentazocine while sigma-2 receptors were labelled with [3H] 1,3-di-o-tolylguanidine (DTG) in the presence of 0.5 microM (+)-pentazocine to mask sigma-1 sites. Non-specific binding was determined in the presence of 20 microM haloperidol. Scatchard analysis revealed a 27% (p<0.01) decreased in sigma-1 receptor density and a 33% (p<0.01) decreased in sigma-2 receptor density in whole brain of 10-week STZ-diabetic rats. No statistically significant difference was found in the sigma receptor content of 5-week STZ-diabetic rats. These results provide evidence that neuronal sigma receptors are reduced in 10-week STZ-diabetic rats and suggest that changes in sigma receptors may play a role in diabetes related abnormalities. Further evaluation is required to determine whether changes observed in the brain are homogeneous for either or both sigma receptor subtypes as well as potential links between other CNS receptor changes previously observed in STZ-induced diabetic rats.
为研究糖尿病对σ受体密度的影响，在5周龄和10周龄对照大鼠以及链脲佐菌素（STZ）诱导的糖尿病大鼠的全脑匀浆膜中进行了体外结合实验。用3H-喷他佐辛标记σ-1受体，而在0.5微摩尔（+）-喷他佐辛存在下用[3H]1,3-二邻甲苯基胍（DTG）标记σ-2受体以掩盖σ-1位点。在20微摩尔氟哌啶醇存在下测定非特异性结合。Scatchard分析显示，10周龄STZ糖尿病大鼠全脑中σ-1受体密度降低27%（p<0.01），σ-2受体密度降低33%（p<0.01）。在5周龄STZ糖尿病大鼠的σ受体含量中未发现统计学上的显著差异。这些结果提供了证据，表明10周龄STZ糖尿病大鼠的神经元σ受体减少，并表明σ受体的变化可能在糖尿病相关异常中起作用。需要进一步评估以确定在脑中观察到的变化对于σ受体亚型之一或两者是否是均匀的，以及先前在STZ诱导的糖尿病大鼠中观察到的其他中枢神经系统受体变化之间的潜在联系。
