Effects of parathyroid hormone on cytosolic calcium of rat adipocytes.
Effects of parathyroid hormone on cytosolic calcium of rat adipocytes.
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DOI：
10.1210/endo.135.5.7525254
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发表时间：
1994-11
期刊：
影响因子：
4.8
通讯作者：
Z. Ni;M. Smogorzewski;S. Massry
中科院分区：
文献类型：
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作者：
Z. Ni;M. Smogorzewski;S. Massry
现有数据表明，脂肪细胞是甲状旁腺素作用的靶点，长期过量的甲状旁腺素增加了脂肪组织的钙负荷，提示甲状旁腺素增加了钙进入脂肪细胞。本研究检测了PTH-(1-84)及其氨基末端片段PTH-(1-34)对脂肪细胞胞浆钙([Ca~(2+)]i)的影响，并探讨了PTH对这些细胞[Ca~(2+)]_i潜在影响的细胞途径。PTH-(1-84)使脂肪细胞[Ca~(2+)]i呈剂量依赖性升高，而PTH-(1-34)无此作用。这一效应发生在有或无钙的培养液中，但当培养液中有钙时，[Ca~(2+)]i的升高幅度明显更大。甲状旁腺激素拮抗剂[Nle8，18Tyr34]bpth(7-34)NH2、维拉帕米和硝苯地平均不同程度地阻断甲状旁腺素引起的[Ca~(2+)]_i升高，佛波酯12-O-十四酰佛波醇-13-乙酸酯和GTP结合蛋白(G蛋白)GTP-γS也使[Ca~(2+)]_i呈剂量依赖性升高。这些作用分别被星状孢子素和G蛋白抑制剂鸟苷5‘-O-1(2-硫代二磷酸)所抑制。同样，星状孢子素、钙磷蛋白C、鸟苷5‘-O-1(2-硫代二磷酸)和百日咳毒素可抑制PTH对脂肪细胞[Ca~(2+)]i的影响。(BU)2cAMP也可使脂肪细胞[Ca~(2+)]_i升高，但PTH不能刺激脂肪细胞产生cAMP，蛋白激酶A的抑制剂N-[2(p-bromocin-namylamino)ethyl]5-isoquinoline-sulfonamide，不影响PTH诱导的脂肪细胞[Ca~(2+)]_i升高。结果表明：1)PTH-(1-84)可使脂肪细胞[Ca~(2+)]_i升高；2)这种激素的作用是由受体介导的；3)激素通过G蛋白激活钙通道和磷脂酶C途径来调节其对[Ca~(2+)]_i的作用；(4)[Ca~(2+)]_i的升高既是由于钙内流增加，又是由于细胞内钙的动员。
Available data indicate that adipocytes are targets for PTH action, and chronic excess of PTH increases calcium burden of fat tissue, suggesting that PTH increases entry of calcium into adipocytes. The present study examined the effects of PTH-(1-84) and its amino-terminal fragment, PTH-(1-34), on cytosolic calcium ([Ca2+]i) of adipocytes and evaluated the cellular pathways that mediate the potential effect of PTH on [Ca2+]i of these cells. PTH-(1-84) but not PTH-(1-34) produced a dose-dependent rise in [Ca2+]i of adipocytes. This effect occurred in the presence or absence of calcium in the media, but the magnitude of the rise in [Ca2+]i was significantly greater when calcium was present in the media. The PTH antagonist [Nle8,18Tyr34]bPTH(7-34)NH2, verapamil, and nifedipine blocked to variable degrees the PTH-induced rise in [Ca2+]i. The phorbol ester 12-O-tetradecanoyl phorbol-13-acetate, and the GTP-binding protein (G protein) GTP gamma S also produced a dose-dependent rise in [Ca2+]i of adipocytes. These effects were inhibited by staurosporine and the G protein inhibitor guanosine 5'-O-1(2-thiodiphosphate), respectively. Similary, staurosporine, calphostin C, guanosine 5'-O-1(2-thiodiphosphate), and pertussis toxin inhibited the effect of PTH on [Ca2+]i of adipocytes. (Bu)2cAMP also increased [Ca2+]i of adipocytes, but PTH did not stimulate cAMP production by adipocytes, and N-[2(p-bromocin-namylamino)ethyl]5-isoquinoline-sulfonamide, an inhibitor of protein kinase A, did not affect the PTH-induced rise in [Ca2+]i of adipocytes. The data indicate that: 1) PTH-(1-84) increases [Ca2+]i of adipocytes; 2) this action of the hormone is receptor mediated; 3) the hormone uses a G protein activation of calcium channels and the phospholipase C pathway in mediating its action on [Ca2+]i; and 4) the rise in [Ca2+]i is due to both increased calcium influx into the adipocytes and mobilization of calcium from intracellular stores.