Bhargava H N, Ramarao P, Gulati A
Department of Pharmacodynamics, University of Illinois, Chicago.
Pharmacology. 1988;37(6):356-64. doi: 10.1159/000138489.
The effect of chronic administration of methimazole (0.05% w/v) in drinking water for 32 days to male Sprague-Dawley rats on the binding of opioid ligands, 3H-Tyr-D-Ala-Gly-MePhe-Gly-ol (DAGO, mu-receptors), 3H-Tyr-D-Ser-Gly-Phe-Leu-Thr (DSTLE, delta-receptors) and 3H-ethylketocyclazocine (EKC, kappa-receptors) to membranes of brain regions was determined. Chronic administration of methimazole to rats decreased their rate of body weight gain, colonic temperature, systolic blood pressure and heart rate in comparison to vehicle-treated rats. Administration of methimazole also decreased the serum concentration of triiodothyronine (total T3) and T4 when compared to vehicle-treated rats. The binding of 3H-DAGO to membranes of amygdala, pons and medulla, striatum, midbrain and cortex of methimazole-treated rats was greater than vehicle-treated rats, however, the binding to membranes of hypothalamus in the two treatment groups did not differ. The binding of 3H-DSTLE in amygdala and hypothalamus of methimazole-treated rats did not differ but it was significantly greater in pons and medulla, midbrain, cortex and striatum of methimazole-treated rats than vehicle-treated rats. The binding of 3H-EKC to membranes of pons and medulla was lower and of striatum and cortex of methimazole-treated rats was significantly greater than vehicle-treated rats, but the binding to membranes of amygdala, hypothalamus, and midbrain of the two treatment groups did not differ. The results indicate that brain, mu-, delta- and kappa-opioid receptors are differentially altered in hypothyroidism.
将甲巯咪唑（0.05% w/v）添加到雄性斯普拉格-道利大鼠的饮用水中，连续给药32天，研究其对阿片样物质配体3H-酪氨酸-D-丙氨酸-甘氨酸-甲基苯丙氨酸-甘醇（DAGO，μ受体）、3H-酪氨酸-D-丝氨酸-甘氨酸-苯丙氨酸-亮氨酸-苏氨酸（DSTLE，δ受体）和3H-乙基酮环唑辛（EKC，κ受体）与脑区膜结合的影响。与给予赋形剂的大鼠相比，对大鼠长期给予甲巯咪唑会降低其体重增加率、结肠温度、收缩压和心率。与给予赋形剂的大鼠相比，给予甲巯咪唑还会降低血清三碘甲状腺原氨酸（总T3）和T4的浓度。给予甲巯咪唑的大鼠杏仁核、脑桥和延髓、纹状体、中脑和皮质膜上3H-DAGO的结合量大于给予赋形剂的大鼠，然而，两个治疗组下丘脑膜上的结合量没有差异。给予甲巯咪唑的大鼠杏仁核和下丘脑膜上3H-DSTLE的结合量没有差异，但在给予甲巯咪唑的大鼠脑桥和延髓、中脑、皮质和纹状体膜上的结合量显著大于给予赋形剂的大鼠。给予甲巯咪唑的大鼠脑桥和延髓膜上3H-EKC的结合量较低，纹状体和皮质膜上的结合量显著大于给予赋形剂的大鼠，但两个治疗组杏仁核、下丘脑和中脑膜上的结合量没有差异。结果表明，甲状腺功能减退时脑内μ、δ和κ阿片受体发生不同程度的改变。
