Villalobos-Molina R, Joseph J A, Rabin B M, Kandasamy S B, Dalton T K, Roth G S
Gerontology Research Center, National Institute on Aging, National Institutes of Health, Baltimore, Maryland 21224.
Radiat Res. 1994 Dec;140(3):382-6.
Initial findings from our laboratory have indicated that muscarinic enhancement of K(+)-evoked release of dopamine from perifused striatal slices is reduced after exposure to 56Fe-particle irradiation. This finding suggested that there is a radiation-induced deficit in muscarinic receptor sensitivity. Subsequent findings have indicated that at least part of the loss in sensitivity may occur as a result of alterations in the initial steps of the signal transduction process and involve muscarinic receptor-G protein coupling/uncoupling. The present study was carried out to localize this deficit further by determining carbachol-stimulated low-Km guanosine triphosphatase (GTPase) activity in striatal and hippocampal tissue obtained from rats exposed to 0, 0.1 or 1.0 Gy of 56Fe-particle irradiation. In addition, to examine the specificity of the effect of 56Fe-particle irradiation, alpha 1-adrenergic-stimulated low-Km GTPase activity was also examined in these tissues. The results showed that there was a high degree of specificity in the effects of 56Fe particles. Decrements were observed in muscarinic-stimulated low-Km GTPase in striatum but not in hippocampus, and 56Fe-particle irradiation did not affect alpha 1-adrenergic low-Km GTPase activity in either brain tissue.
我们实验室的初步研究结果表明，在暴露于56Fe粒子辐射后，毒蕈碱增强从灌注的纹状体切片中K(+)诱发的多巴胺释放的作用减弱。这一发现表明存在辐射诱导的毒蕈碱受体敏感性缺陷。随后的研究结果表明，至少部分敏感性丧失可能是由于信号转导过程初始步骤的改变所致，并且涉及毒蕈碱受体-G蛋白偶联/解偶联。本研究通过测定从接受0、0.1或1.0 Gy 56Fe粒子辐射的大鼠获得的纹状体和海马组织中卡巴胆碱刺激的低Km鸟苷三磷酸酶（GTP酶）活性，进一步确定这种缺陷的定位。此外，为了研究56Fe粒子辐射作用的特异性，还检测了这些组织中α1-肾上腺素能刺激的低Km GTP酶活性。结果表明，56Fe粒子的作用具有高度特异性。在纹状体中观察到毒蕈碱刺激的低Km GTP酶活性降低，但在海马中未观察到，并且56Fe粒子辐射对两种脑组织中的α1-肾上腺素能低Km GTP酶活性均无影响。
