甲状旁腺激素（PTH）和甲状旁腺激素相关蛋白（PTHrP）对负鼠肾（OK）细胞中环磷酸腺苷（cAMP）积累和磷酸盐摄取的解离作用
Dissociation of cAMP accumulation and phosphate uptake in opossum kidney (OK) cells with parathyroid hormone (PTH) and parathyroid hormone related protein (PTHrP).
作者信息
Muff R, Caulfield M P, Fischer J A
机构信息
Department of Orthopedic Surgery and Medicine, University of Zurich, Switzerland.
出版信息
Peptides. 1990 Sep-Oct;11(5):945-9. doi: 10.1016/0196-9781(90)90014-v.
Bovine parathyroid hormone (PTH) 1-34 [bPTH(1-34)] and human PTH related protein [hPTHrP(1-34)] stimulated cAMP accumulation in opossum kidney (OK) cells with Km of 5 x 10(-9) M, but inhibition of phosphate uptake was obtained with 17-fold lower Km of 3 x 10(-10) M. Phosphate uptake was partially inhibited with [Nle8.18Tyr34]bPTH(3-34)NH2 without concomitant cAMP stimulation. With hPTHrP(7-34)NH2, cAMP accumulation was increased in parallel to inhibition of phosphate uptake. [D-Trp12Tyr34]bPTH(7-34)NH2 and [Tyr34]hPTH(7-34)NH2 had no agonist activity on cellular cAMP and inhibition of phosphate uptake. bPTH(1-34)-stimulated cAMP accumulation was antagonized by [Nle8.18Tyr34]bPTH(3-34)NH2, [D-Trp12Tyr34]bPTH(7-34)NH2, hPTHrP(7-34)NH2 and [Tyr34]hPTH(7-34)NH2 with Ki of 1.4 x 10(-7), 2 x 10(-7), 4.7 x 10(-7) and 3.7 x 10(-6) M, respectively. But [Nle8.18Tyr34]bPTH(3-34)NH2 and [D-Trp12Tyr34]bPTH(7-34)NH2 reversed the inhibition of phosphate uptake only marginally, and hPTHrP(7-34)NH2 and [Tyr34]hPTH(7-34)NH2 were inactive. With hPTHrP(1-34) the Ki for cAMP accumulation of [Nle8,18Tyr34]bPTH(3-34)NH2 and hPTHrP(7-34)NH2 were 1.9 x 10(-7) and 7.2 x 10(-7) M, and inhibition of phosphate uptake was partially reversed with [Nle8,18Tyr34]bPTH(3-34)NH2, but not with hPTHrP(7-34)NH2. The present results indicate that truncated hPTHrP(7-34)NH2, unlike [Tyr34]hPTH(7-34)NH2 and [D-Trp12Tyr34]bPTH(7-34)NH2, elevates cellular cAMP and inhibits phosphate uptake. bPTH(1-34)- and hPTHrP(1-34)-evoked cAMP accumulation is suppressed by PTH and PTHrP fragments while inhibition of phosphate uptake remains largely unaltered.
牛甲状旁腺激素（PTH）1 - 34 [bPTH(1 - 34)]和人甲状旁腺激素相关蛋白[hPTHrP(1 - 34)]刺激负鼠肾（OK）细胞中cAMP积累，其Km为5×10⁻⁹ M，但对磷酸盐摄取的抑制作用在Km为3×10⁻¹⁰ M时即可出现，后者比前者低17倍。[Nle8.18Tyr34]bPTH(3 - 34)NH₂可部分抑制磷酸盐摄取，同时不伴随cAMP刺激。对于hPTHrP(7 - 34)NH₂，cAMP积累的增加与磷酸盐摄取的抑制呈平行关系。[D - Trp12Tyr34]bPTH(7 - 34)NH₂和[Tyr34]hPTH(7 - 34)NH₂对细胞cAMP和磷酸盐摄取抑制均无激动剂活性。bPTH(1 - 34)刺激的cAMP积累受到[Nle8.18Tyr34]bPTH(3 - 34)NH₂、[D - Trp12Tyr34]bPTH(7 - 34)NH₂、hPTHrP(7 - 34)NH₂和[Tyr34]hPTH(7 - 34)NH₂的拮抗作用，其Ki分别为1.4×10⁻⁷、2×10⁻⁷、4.7×10⁻⁷和3.7×10⁻⁶ M。但是，[Nle8.18Tyr34]bPTH(3 - 34)NH₂和[D - Trp12Tyr34]bPTH(7 - 34)NH₂仅轻微逆转磷酸盐摄取的抑制作用，而hPTHrP(7 - 34)NH₂和[Tyr34]hPTH(7 - 34)NH₂则无活性。对于hPTHrP(1 - 34)，[Nle8,18Tyr34]bPTH(3 - 34)NH₂和hPTHrP(7 - 34)NH₂对cAMP积累的Ki分别为1.9×10⁻⁷和7.2×10⁻⁷ M，[Nle8,18Tyr34]bPTH(3 - 34)NH₂可部分逆转磷酸盐摄取的抑制作用，而hPTHrP(7 - 34)NH₂则不能。目前的结果表明，截短的hPTHrP(7 - 34)NH₂与[Tyr34]hPTH(7 - 34)NH₂和[D - Trp12Tyr34]bPTH(7 - 34)NH₂不同，它可提高细胞内cAMP水平并抑制磷酸盐摄取。PTH和PTHrP片段可抑制bPTH(1 - 34)和hPTHrP(1 - 34)引起的cAMP积累，而对磷酸盐摄取抑制作用的影响则不大。
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