Kaasik A, Seppet E K, Ohisalo J J
Department of Pathophysiology, University of Tartu, Estonia.
J Mol Cell Cardiol. 1994 Apr;26(4):509-17. doi: 10.1006/jmcc.1994.1061.
Left atria were isolated from rats made hypothyroid by adding propylthiouracil to their drinking water, such rats after saturating doses of thyroid hormones, and from control rats. Isoproterenol (ISO; 1 microM) increased the values of developed tension (DT), maximal rate of tension development (+dt/dt) and tension fall (-dT/dt). The effect was largest in hypothyroid and lowest in hyperthyroid atria. The adenosine A1-receptor agonist N6-(phenylisopropyl)-adenosine (PIA) had a powerful negative inotropic effect in ISO-stimulated atria. The effects of PIA on +dT/dt, -dT/dt and DT were enhanced in hypothyroidism. Adenosine receptor number was not decreased. The amount of total Gi-like proteins was estimated by pertussis toxin labeling. The amounts of Gi2 and Gi3 were estimated in Western blots using such antisera raised in rabbits against peptides corresponding to parts of their sequences, using purified recombinant alpha subunits as standards. The amounts of low and high molecular weight forms of Gs were estimated by cholera toxin labeling Gi2, Gi3 and pertussis toxin substrate concentrations were slightly lower in the hypothyroid animals, while the amounts of both forms of Gs per mg of protein were only half of those in euthyroid rat atria. The levels of Gi2 and Gi3 were greatly elevated as compared to Gs as membrane marker. These changes were reversed by treatment of the hypothyroid rats with thyroid hormones. In conclusion, the present results show an enhanced negative inotropic effect of an adenosine.(ABSTRACT TRUNCATED AT 250 WORDS)
从通过在饮用水中添加丙硫氧嘧啶制成甲状腺功能减退的大鼠、给予饱和剂量甲状腺激素后的此类大鼠以及对照大鼠中分离出左心房。异丙肾上腺素（ISO；1微摩尔）增加了舒张期张力（DT）、最大张力发展速率（+dt/dt）和张力下降速率（-dT/dt）的值。该效应在甲状腺功能减退的心房中最大，在甲状腺功能亢进的心房中最小。腺苷A1受体激动剂N6-（苯异丙基）-腺苷（PIA）在ISO刺激的心房中具有强大的负性肌力作用。PIA对+dt/dt、-dT/dt和DT的作用在甲状腺功能减退时增强。腺苷受体数量未减少。通过百日咳毒素标记估计总Gi样蛋白的量。使用针对与其序列部分相对应的肽在兔中产生的抗血清，通过蛋白质印迹法估计Gi2和Gi3的量，使用纯化的重组α亚基作为标准。通过霍乱毒素标记估计Gs的低分子量和高分子量形式的量。甲状腺功能减退动物中Gi2、Gi3和百日咳毒素底物浓度略低，而每毫克蛋白质中两种形式的Gs的量仅为正常甲状腺大鼠心房中的一半。与作为膜标记物的Gs相比，Gi2和Gi3的水平大大升高。用甲状腺激素治疗甲状腺功能减退大鼠可逆转这些变化。总之，目前的结果表明腺苷的负性肌力作用增强。（摘要截短至250字）
