Yamamoto Y, Fukase M, Fujii Y, Fujita T
Department of Medicine, Kobe University School of Medicine, Japan.
Bone Miner. 1989 Nov;7(3):221-31. doi: 10.1016/0169-6009(89)90079-2.
The effects of three synthetic amino-terminal fragments of human parathyroid hormone-related peptide (hPTHrP) on cytosolic free calcium ([Ca2+]i) mobilization and intracellular cAMP production were investigated and compared with those of human PTH(1-34) in opossum kidney (OK) cells. The mean basal [Ca2+]i in OK cells was 115 +/- 7.8 nM (mean +/- SE, n = 30). Human PTHrP(1-34), [40Tyr]hPTHrP(1-40) and hPTH(1-34) significantly (P less than 0.01) raised [Ca2+]i to 149 +/- 3, 150 +/- 5 and 148 +/- 6% of the basal value, respectively (mean +/- SE, n = 3). These three peptides showed similar dose dependency at concentrations between 10(-10) and 10(-7) M. These increases appeared to be, in part, due to mobilization from intracellular calcium stores. On the other hand, these three peptides also stimulated intracellular cAMP production in an equipotent manner in OK cells. However, both 10(-3) M dibutyryl cAMP and 10(-5) M forskolin failed to cause an increase in [Ca2+]i. Furthermore, [40Tyr]hPTHrP(3-40) neither affected the intracellular cAMP content significantly nor caused an increase in [Ca2+]i. These results indicate that hPTHrP mimics PTH by activating a dual second messenger system ([Ca2+]i and cAMP) in OK cells, and that [Ca2+]i stimulation by hPTHrP and hPTH is independent of cAMP production. Additionally, N-terminal amino acid position 1 to 2 of hPTHrP appears to play a crucial role in both [Ca2+]i stimulation and cAMP production.
研究了人甲状旁腺激素相关肽（hPTHrP）的三个合成氨基末端片段对负鼠肾（OK）细胞胞质游离钙（[Ca2+]i）动员和细胞内cAMP产生的影响，并与人生长激素释放肽（1-34）进行了比较。OK细胞中的平均基础[Ca2+]i为115±7.8 nM（平均值±标准误，n = 30）。人PTHrP（1-34）、[40Tyr]hPTHrP（1-40）和hPTH（1-34）分别显著（P<0.01）将[Ca2+]i提高至基础值的149±3%、150±5%和148±6%（平均值±标准误，n = 3）。这三种肽在10(-10)至10(-7)M的浓度下表现出相似的剂量依赖性。这些增加似乎部分是由于细胞内钙库的动员。另一方面，这三种肽在OK细胞中也以等效方式刺激细胞内cAMP产生。然而，10(-3)M二丁酰cAMP和10(-5)M福司可林均未能导致[Ca2+]i增加。此外，[40Tyr]hPTHrP(3-40)既未显著影响细胞内cAMP含量，也未导致[Ca2+]i增加。这些结果表明，hPTHrP通过激活OK细胞中的双第二信使系统（[Ca2+]i和cAMP）来模拟PTH，并且hPTHrP和hPTH对[Ca2+]i的刺激独立于cAMP产生。此外，hPTHrP的N末端氨基酸位置1至2似乎在[Ca2+]i刺激和cAMP产生中都起着关键作用。
