Bliziotes M M, Lewis S B, Licht J H
Endocrinology. 1982 Nov;111(5):1657-62. doi: 10.1210/endo-111-5-1657.
We examined the effect of indomethacin (INDO) on PTH-stimulated cAMP release from the perfused rat hindlimb. Since this preparation has not been used previously to study the effects of PTH, we first determined the dose-response curve for cAMP release in response to the 1-34 fragment of synthetic bovine PTH. cAMP release peaked 3-6 min after the PTH bolus and declined gradually toward baseline, even with sustained PTH infusion. The rate of cAMP release was directly related to the PTH dose. The lowest PTH priming dose that provoked a significant increase in cAMP release was 0.6 IU. Maximal cAMP release, occurring in response to a PTH priming dose of 30 IU, was 3- to 4-fold greater than baseline. PTH caused no increase in cAMP release from or the cAMP content of isolated skeletal muscle in vitro, suggesting that cAMP released from the hindlimb in response to PTH is derived solely from bone. PTH-stimulated cAMP release was unaltered by pretreatment of the intact rat with 2 mg/kg INDO, a dose that blocks prostaglandin synthesis. In contrast, PTH-stimulated cAMP release was significantly attenuated by pretreatment with 75 mg/kg INDO. The effect was not dependent on the addition of drug to the perfusate and was not altered by thyroparathyroidectomy at the time of INDO administration. We conclude that 1) the perfused rat hindlimb can be used to examine PTH effects on bone; 2) 2 mg/kg INDO has no effect on PTH-stimulated cAMP release from the perfused rat hindlimb; and 3) INDO in high doses blunts PTH activation of adenylate cyclase.
我们研究了吲哚美辛（INDO）对灌注大鼠后肢甲状旁腺激素（PTH）刺激的环磷酸腺苷（cAMP）释放的影响。由于此前未使用该制备方法来研究PTH的作用，我们首先确定了合成牛PTH 1-34片段刺激cAMP释放的剂量反应曲线。PTH推注后3-6分钟cAMP释放达到峰值，即使持续输注PTH，也会逐渐下降至基线水平。cAMP释放速率与PTH剂量直接相关。引起cAMP释放显著增加的最低PTH起始剂量为0.6国际单位（IU）。响应30 IU的PTH起始剂量时出现的最大cAMP释放比基线水平高3至4倍。PTH在体外未引起分离的骨骼肌中cAMP释放增加或cAMP含量增加，这表明后肢响应PTH释放的cAMP仅来源于骨骼。用2 mg/kg INDO预处理完整大鼠（该剂量可阻断前列腺素合成），并未改变PTH刺激的cAMP释放。相反，用75 mg/kg INDO预处理可显著减弱PTH刺激的cAMP释放。该作用不依赖于向灌注液中添加药物，且在给予INDO时进行甲状旁腺切除术也不会改变。我们得出以下结论：1）灌注大鼠后肢可用于研究PTH对骨骼的作用；2）2 mg/kg INDO对灌注大鼠后肢PTH刺激的cAMP释放无影响；3）高剂量的INDO可减弱PTH对腺苷酸环化酶的激活作用。
