MEMBRANES FROM A TRANSPLANTABLE OSTEOGENIC-SARCOMA RESPONSIVE TO PARATHYROID-HORMONE AND PROSTAGLANDINS - REGULATION OF ADENYLATE-CYCLASE AND OF HORMONE METABOLISM
MEMBRANES FROM A TRANSPLANTABLE OSTEOGENIC-SARCOMA RESPONSIVE TO PARATHYROID-HORMONE AND PROSTAGLANDINS - REGULATION OF ADENYLATE-CYCLASE AND OF HORMONE METABOLISM
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DOI：
10.1677/joe.0.0770213
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发表时间：
1978-01-01
影响因子：
4
通讯作者：
MARTIN, TJ
中科院分区：
文献类型：
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作者：
CRAWFORD, A;HUNT, NH;MARTIN, TJ
腺苷酸环化酶活性的颗粒馏分从可移植的大鼠成骨肉瘤的刺激，在剂量依赖性的方式由前列腺素E1和E2（PGE 1和PGE 2）和甲状旁腺激素（PTH）。前列腺素F2 α在高浓度（3 × 10 - 4）下具有活性。10-4 mol/l）。用胶原酶加透明质酸酶预处理膜降低了PTH效应的大小，但不影响PGE 1效应的大小。GTP及其合成类似物5“-鸟苷酰亚氨二磷酸（Gpp（NH）p）激活成骨肉瘤颗粒制剂中的腺苷酸环化酶。后一种药剂产生更大的效果，尽管两种激动剂的半最大酶激活所需的浓度相同（大约2 ×10-6 mol/l）。在某些激素浓度下，PTH和Gpp（NH）p的作用是超加性的。PGE 1和Gpp（NH）p的影响在所有激素浓度下都是超加性的。用PTH预孵育膜颗粒6分钟产生酶活化，其通过洗涤稀释不会逆转。与PGE 1预孵育没有产生这种效果。膜腺苷酸环化酶的GPP（NH）p（10-4 mol/L）的反应是75%以上的制备与PTH比在膜预孵育单独的缓冲液或缓冲液中含有PGE 1。腺苷酸环化酶测定系统中环[c]AMP产生的基础速率在35分钟孵育期内下降。这种减少是通过添加PTH或PGE 1来防止的。加入NaF或Gpp（NH）p可使cAMP的生成速率随时间稳定增加。膜制剂没有降低PTH的生物活性，也没有降解125 I标记的PTH。成骨肉瘤的PTH和PGE反应性腺苷酸环化酶具有明显不同的性质，肿瘤的颗粒制剂不代谢PTH。
Adenylate cyclase activity in particulate fractions from a transplantable rat osteogenic sarcoma was stimulated in a dose-dependent manner by prostaglandins E1 and E2 (PGE1 and PGE2) and parathyroid hormone (PTH). Prostaglandin F2.alpha. was active at a high concentration (3 .times. 10-4 mol/l). Pretreatment of membranes with collagenase plus hyaluronidase reduced the magnitude of the PTH effect but did not affect the size of the PGE1 effect. GTP and its synthetic analog 5''-guanylylimidodiphosphate (Gpp(NH)p) activated adenylate cyclase in particulate preparations from the osteogenic sarcoma. The latter agent produced larger effects, although the concentrations required for half-maximal enzyme activation were the same for both agonists (approximately 2 .times. 10-6 mol/l). The effects of PTH and Gpp(NH)p were supra-additive at some concentrations of hormone. The effects of PGE1 and Gpp(NH)p were supra-additive at all hormone concentrations tested. Preincubation of membrane particles for 6 min with PTH produced enzyme activation which was not reversed by dilution through washing. Preincubation with PGE1 did not produce this effect. The response of membrane adenylate cyclase to Gpp(NH)p (10-4 mol/l) was 75% greater in preparations preincubated with PTH than in membranes preincubated in buffer alone or buffer containing PGE1. The basal rate of cyclic[c]AMP production in the adenylate cyclase assay system decreased over a 35 min incubation period. This decrease was prevented by addition of PTH or PGE1. Addition of NaF or Gpp(NH)p produced a steady increase in the rate of production of cAMP with time. Membrane preparations did not reduce the biological activity of PTH and did not degrade 125I-labeled PTH. The PTH- and PGE-responsive adenylate cyclases of the osteogenic sarcoma have distinctly different properties and particulate preparations of the tumor do not metabolize PTH.