Influence of the amino-terminus on in vitro and in vivo biological activity of synthetic parathyroid hormone-like peptides of malignancy.
Influence of the amino-terminus on in vitro and in vivo biological activity of synthetic parathyroid hormone-like peptides of malignancy.
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氨基末端对合成甲状旁腺激素样恶性肿瘤肽的体外和体内生物活性的影响。
DOI：
10.1210/endo-123-6-2709
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发表时间：
1988
期刊：
影响因子：
4.8
通讯作者：
David Goltzman
中科院分区：
文献类型：
--
作者：
A. Rabbanis;Jane Mitchell;Denis Roy;G. Hendy;David Goltzman
我们比较了与恶性肿瘤相关的人（h）PTH样肽（PLP）的合成截短的NH 2-末端片段[hPLP-（3-34）]、完整的NH 2-末端片段[hPLP-（1-34）]和PTH的NH 2-末端片段[hPTH-（1-34）]的生物活性。虽然hPLP-（1-34）在刺激大鼠肾膜中腺苷酸环化酶方面不如hPTH-（1-34）有效，但hPLP-（1-34）和hPTH-（1-34）在体外刺激OK肾细胞以及UMR 108骨肉瘤细胞中腺苷酸环化酶方面是等效的。在骨肉瘤细胞中，这些肽中的每一种都可以使腺苷酸环化酶对自身和其他肽的反应脱敏，但不能减少前列腺素E2的刺激。维生素D缺乏大鼠继发性甲状旁腺功能亢进的肾膜减少PLP刺激以及PTH刺激的腺苷酸环化酶反应。截短的类似物hPLP-（3-34）在体外仅为弱的部分激动剂和拮抗剂，在肾和骨细胞中产生与hPLP-（1-34）和hPTH-（1-34）相当的抑制，并且不能使激动剂反应脱敏。在体内甲状腺甲状旁腺切除大鼠中，hPLP-（1-34）和hPTH-（1-34）增加cAMP排泄，增强磷酸盐尿，维持血浆钙，并减少钙尿。等摩尔浓度的hPLP-（3-34）未产生高于对照水平的增加;然而，高浓度的该肽模拟PTH对肾和血浆离子处理的作用，同时适度增加cAMP排泄。这些结果证明了PLP的前两个残基对于生物活性的重要性，表明PLP和PTH在体内以及体外在共同受体位点相互作用，表明PLP在肾靶细胞中的效力可能不低于PTH，并表明这些肽与其在靶组织中的共同受体相互作用的净结果可能反映受体介导的事件的活化和脱敏。
We compared the bioactivities of a synthetic truncated NH2-terminal fragment of the human (h) PTH-like peptide (PLP) associated with malignancies [hPLP-(3-34)], an intact NH2-terminal fragment [hPLP-(1-34)], and an NH2-terminal fragment of PTH [hPTH-(1-34)]. Although hPLP-(1-34) was less potent than hPTH-(1-34) in stimulating adenylate cyclase in rat renal membranes, hPLP-(1-34) and hPTH-(1-34) were equipotent in stimulating adenylate cyclase in OK renal cells as well as in UMR 108 osteosarcoma cells in vitro. In osteosarcoma cells, each of these peptides could desensitize adenylate cyclase responses to itself and to the other peptide, but could not reduce stimulation by prostaglandin E2. Renal membranes of vitamin D-deficient rats with secondary hyperparathyroidism had a reduced PLP-stimulated as well as PTH-stimulated adenylate cyclase response. The truncated analog hPLP-(3-34) was only a weak partial agonist and an antagonist in vitro, produced equivalent inhibition of hPLP-(1-34) and hPTH-(1-34) in renal and osseous cells, and could not desensitize agonist responses. In thyroparathyroidectomized rats in vivo, hPLP-(1-34) and hPTH-(1-34) increased cAMP excretion, enhanced phosphaturia, maintained plasma calcium, and reduced calciuria. Equimolar concentrations of hPLP-(3-34) produced no increases above control levels; however, high concentrations of this peptide mimicked PTH actions on renal and plasma ion handling while modestly augmenting cAMP excretion. These results demonstrate the importance of the first two residues of PLP for bioactivity, indicate that PLP and PTH interact at common receptor sites in vivo as well as in vitro, suggest that PLP may not be less potent than PTH in renal target cells, and indicate that the net result of interaction of these peptides with their common receptor in target tissues may reflect both activation and desensitization of receptor-mediated events.
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甲状旁腺激素相关蛋白的合成肽对啮齿动物体内和体外钙稳态、肾小管钙重吸收和骨代谢的影响。
DOI：
10.1172/jci113406
发表时间：
1988
期刊：
The Journal of clinical investigation
影响因子：
--
作者：
Yates,AJ;Gutierrez,GE;Smolens,P;Travis,PS;Katz,MS;Aufdemorte,TB;Boyce,BF;Hymer,TK;Poser,JW;Mundy,GR
通讯作者：
Mundy,GR
狗体内甲状旁腺激素拮抗剂的体外评价。
影响因子：
4.8
作者：
Segre,GV;Rosenblatt,M;Tully3rd,GL;Laugharn,J;Reit,B;PottsJr,JT
通讯作者：
PottsJr,JT
影响因子：
4.8
作者：
A. Teitelbaum;G. Strewler
通讯作者：
A. Teitelbaum;G. Strewler
人类肿瘤合成肽与甲状旁腺激素在体内和体外的相似性。
DOI：
10.1126/science.3685994
发表时间：
1987
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Horiuchi,N;Caulfield,MP;Fisher,JE;Goldman,ME;McKee,RL;Reagan,JE;Levy,JJ;Nutt,RF;Rodan,SB;Schofield,TL
通讯作者：
Schofield,TL
DOI：
10.1172/jci110825
发表时间：
1983-03
期刊：
The Journal of clinical investigation
影响因子：
--
作者：
G. Strewler;R. Williams;R. Nissenson
通讯作者：
G. Strewler;R. Williams;R. Nissenson