Segal J
Hubert H. Humphrey Center for Experimental Medicine and Cancer Research, Hebrew University-Hadassah Medical School, Jerusalem, Israel.
Endocrinology. 1990 May;126(5):2693-702. doi: 10.1210/endo-126-5-2693.
The thyroid hormone T3 produced a very rapid and transient increase in 45calcium uptake by freshly isolated rat heart slices, which was seen already 15 sec after the addition of the hormone, reached a maximum at 30 sec, and then progressively declined and returned to control values after 10 min. This effect of T3 was independent of extracellular calcium, concentration related (evident at a physiological concentration of 10 pM, reached maximum of about 75% above control at 1 nM, and was smaller at greater concentrations), and thyroid hormone specific, as judged from the order of potency of several thyroid hormone analogs: L-T3 greater than L-T4 greater than or equal to D-T3 greater than 3'-isopropyl-3,5-L-diiodothyronine greater than D-T4 greater than 3,5-L-diiodothyronine greater than r-L-T3 greater than D,L-thyronine. The inorganic calcium channel blockers La3+, Cd2+, and Mn2+ inhibited, in a concentration-related fashion, basal and T3-induced increases in 45Ca uptake in the cardiac slices. The organic calcium channel blockers verapamil, nifedipine, and diltiazem were without effect, indicating that in the quiescent cardiac slice the effect of T3 on 45Ca uptake is independent of sarcolemmal depolarization. Additional studies demonstrated that the stimulatory effect of T3 on 2-deoxyglucose uptake by the cardiac slices required extracellular calcium and was inhibited by the calcium channel blockers La3+, Cd2+, and Mn2+. The present study provides conclusive evidence for two central issues: that calcium is the first messenger for the prompt, plasma membrane-mediated action of thyroid hormone to increase cellular sugar uptake, and that thyroid hormone produces an acute increase in calcium uptake by the heart, an effect that is demonstrable at physiological concentrations and is thyroid hormone specific and, therefore, points to a physiological relevance for this action.
甲状腺激素T3可使新鲜分离的大鼠心脏切片对45钙的摄取迅速且短暂增加，在加入该激素15秒后即可观察到，30秒时达到最大值，随后逐渐下降，10分钟后恢复到对照值。T3的这种作用与细胞外钙无关，与浓度相关（在生理浓度10 pM时明显，在1 nM时比对照值高出约75%达到最大值，更高浓度时作用较小），且具有甲状腺激素特异性，从几种甲状腺激素类似物的效力顺序判断：L-T3大于L-T4大于或等于D-T3大于3'-异丙基-3,5-L-二碘甲腺原氨酸大于D-T4大于3,5-L-二碘甲腺原氨酸大于r-L-T3大于D,L-甲状腺素。无机钙通道阻滞剂La3+、Cd2+和Mn2+以浓度相关的方式抑制心脏切片中基础和T3诱导的45Ca摄取增加。有机钙通道阻滞剂维拉帕米、硝苯地平和地尔硫䓬无效，表明在静止的心脏切片中，T3对45Ca摄取的作用与肌膜去极化无关。进一步研究表明，T3对心脏切片2-脱氧葡萄糖摄取的刺激作用需要细胞外钙，并被钙通道阻滞剂La3+、Cd2+和Mn2+抑制。本研究为两个核心问题提供了确凿证据：钙是甲状腺激素迅速的、通过质膜介导的增加细胞糖摄取作用的第一信使；甲状腺激素使心脏对钙的摄取急性增加，这种作用在生理浓度下可得到证实，具有甲状腺激素特异性，因此表明该作用具有生理相关性。
