Brown K J, Summers R J
Department of Pharmacology, Monash University, 3800, Victoria, Australia.
Eur J Pharmacol. 2001 Mar;415(2-3):257-63. doi: 10.1016/s0014-2999(01)00795-6.
The effect of hypothyroidism on gastrointestinal beta(1)- and beta(3)-adrenoceptor function and expression was examined in rat ileal smooth muscle preparations. (-)-Isoprenaline and the selective beta(3) agonist disodium (R,R)-5-[2-[[2-3-chlorophenyl)-2-hydroxyethyl]-amino]propyl]-1,3-benzodioxole-2,2-dicarboxylate (CL 316234) relaxed both control and hypothyroid tissues in a dose-dependent manner. Responses to isoprenaline were reduced in tissues from hypothyroid rats, as was the shift produced with the beta(3)-adrenoceptor antagonist, 3-(2-ethylphenoxy)-1-[(1S)-1,2,3,4-tetrahydronaphth-1-ylamino]-(2S)-2-propanol oxalate (SR 59230A). No change was seen in responses to CL 316243. Experiments with a selective beta(1)-adrenoceptor antagonist produced results suggesting that isoprenaline did not act at this receptor. Messenger RNA levels for both beta(1)- and beta(2)-adrenoceptors were not affected by hypothyroidism. These results show that, unlike in adipose tissues, ileal beta(1)- and beta(3)-adrenoceptors are not directly regulated by thyroid hormone and that beta(3)-adrenoceptor coupling to the relaxation response is reduced in a rat model of hypothyroidism.
在大鼠回肠平滑肌制备物中研究了甲状腺功能减退对胃肠道β1和β3肾上腺素能受体功能及表达的影响。（-）-异丙肾上腺素和选择性β3激动剂（R，R）-5-[2-[[2-（3-氯苯基）-2-羟乙基]氨基]丙基]-1,3-苯并二恶唑-2,2-二羧酸钠（CL 316234）以剂量依赖性方式使对照组织和甲状腺功能减退组织均松弛。甲状腺功能减退大鼠组织对异丙肾上腺素的反应降低，β3肾上腺素能受体拮抗剂3-（2-乙基苯氧基）-1-[(1S)-1,2,3,4-四氢萘-1-基氨基]-(2S)-2-丙醇草酸盐（SR 59230A）产生的偏移也降低。对CL 316243的反应未见变化。用选择性β1肾上腺素能受体拮抗剂进行的实验结果表明异丙肾上腺素不作用于该受体。β1和β2肾上腺素能受体的信使核糖核酸水平不受甲状腺功能减退的影响。这些结果表明，与脂肪组织不同，回肠β1和β3肾上腺素能受体不受甲状腺激素直接调节，并且在甲状腺功能减退大鼠模型中β3肾上腺素能受体与松弛反应的偶联减少。
