Chin J P, Pennefather J N
Department of Pharmacology, Monash University, Clayton, Victoria, Australia.
Eur J Pharmacol. 1992 Mar 3;212(2-3):201-7. doi: 10.1016/0014-2999(92)90330-7.
The potencies of the beta 1-adrenoceptor agonist, noradrenaline, and the beta 2-adrenoceptor agonist, fenoterol, at beta-adrenoceptors in portal vein were examined using preparations isolated from control, methimazole-treated or l-thyroxine-treated rats. Tissues were preincubated with phenoxybenzamine (1 mumol/l) to block alpha-adrenoceptors and neuronal and extraneuronal uptake. Fenoterol was approximately 400 times more potent than noradrenaline (-log IC50 7.85 vs. 5.26) in inhibiting the spontaneous contractions of the portal vein. The beta 2-adrenoceptor antagonist, ICI 118,551, was approximately 3000 fold more potent than the beta 1-adrenoceptor antagonist, atenolol, in blocking the effects of fenoterol (pA2 9.32 and 5.88 respectively) and 400 times more potent in antagonising noradrenaline (pA2 8.96 vs. 6.23). Treatment of rats with methimazole led to decreased myogenic tone, and treatment with thyroxine to increased tone. beta-Adrenoceptor binding densities and the relative potencies of the agonists and antagonists used were unaffected by methimazole treatment. Thyroxine administration was also without effect on the relative potencies of these compounds. Our data indicate that although the portal vein is a target tissue for thyroxine, as indicated by its influence on myogenic tone, the beta-adrenoceptor population in this preparation, confirmed to be of the beta 2-subtype, is unaffected.
使用从对照、甲巯咪唑处理或左旋甲状腺素处理的大鼠分离的制剂，检测了β1肾上腺素能受体激动剂去甲肾上腺素和β2肾上腺素能受体激动剂非诺特罗在门静脉β肾上腺素能受体上的效能。组织预先用酚苄明（1μmol/L）孵育以阻断α肾上腺素能受体以及神经元和非神经元摄取。在抑制门静脉的自发收缩方面，非诺特罗的效能比去甲肾上腺素高约400倍（-log IC50分别为7.85和5.26）。β2肾上腺素能受体拮抗剂ICI 118,551在阻断非诺特罗的作用方面比β1肾上腺素能受体拮抗剂阿替洛尔强约3000倍（pA2分别为9.32和5.88），在拮抗去甲肾上腺素方面强400倍（pA2为8.96对6.23）。用甲巯咪唑治疗大鼠导致肌源性张力降低，用甲状腺素治疗导致张力增加。β肾上腺素能受体结合密度以及所用激动剂和拮抗剂的相对效能不受甲巯咪唑治疗的影响。给予甲状腺素对这些化合物的相对效能也没有影响。我们的数据表明，尽管门静脉是甲状腺素的靶组织，如其对肌源性张力的影响所示，但该制剂中的β肾上腺素能受体群体，经证实为β2亚型，未受影响。
