Parathyroid hormone increases cytosolic calcium of thymocytes.
Parathyroid hormone increases cytosolic calcium of thymocytes.
复制标题
甲状旁腺激素增加胸腺细胞的胞质钙。
作者：
Stojceva-Taneva,O;Fadda,GZ;Smogorzewski,M;Massry,SG
甲状旁腺激素（PTH）与尿毒症免疫系统异常的发生有关。这种作用归因于PTH增加钙进入的能力，从而维持免疫系统细胞中细胞溶质钙（[Ca 2 +]i）的基础水平的升高。然而，缺乏这种激素对这些细胞作用的直接证据。我们研究了甲状旁腺素是否影响大鼠胸腺细胞[Ca ~（2+）] i以及这种作用的可能机制。1-84 PTH（0.5，1.0，2.0 × 10 ~（-7）M）使[Ca ~（2+）] i分别增加31 ± 2.6，73 ± 3.8和128 ± 10.8 nM，呈剂量依赖性。1-34 PTH没有影响。不同剂量的PTH拮抗剂（[Tyr-34] bPTH（7-34）NH_2）阻断PTH诱导的[Ca ~（2+）] i升高41- 67%。二丁酰腺苷3 ′，5 ′-环磷酸酶（cAMP）、佛司可林（forskolin）和佛波酯12-O-十四酰佛波酯13-乙酸酯（TPA）也能使胸腺细胞[Ca ~（2+）] i显著升高。维拉帕米阻断PTH作用44%，但对二丁酰-cAMP-、毛喉素-或TPA-诱导的[Ca 2 +]i升高无影响。培养基中钙的缺乏消除了PTH诱导的[Ca ~（2+）] i的增加，并显着降低了双丁酰cAMP。Staurosprine完全阻止TPA诱导的[Ca 2 +] i升高，但对PTH产生的[Ca 2 +] i无影响。1-84 PTH在培养基中钙的存在下产生胸腺细胞cAMP的显着上升，但在培养基中钙的情况下没有影响。数据表明：（1）胸腺细胞是PTH的靶细胞，完整的激素很可能通过受体-激素相互作用增加其[Ca 2 +]i，（2）激素的这种作用似乎部分由其刺激cAMP生成介导，部分由电压门控钙通道激活介导，（3）[Ca 2 +] i i升高，最可能是由于钙进入胸腺细胞和细胞内钙储存的动员。
Parathyroid hormone (PTH) has been implicated in the genesis of the abnormalities of the immune system in uremia. This action was attributed to the ability of PTH to augment entry of calcium and hence sustain an elevation of the basal level of cytosolic calcium ([Ca2+]i) in the cells of the immune system. However, direct evidence for such an action of the hormone on these cells is lacking. We examined whether PTH affects [Ca2+]iof rat thymocytes and the potential mechanisms of such an effect. 1-84 PTH (0.5,1.0,2.0 × 10-7M) increased [Ca2+]iin a dose-dependent manner by 31 ± 2.6,73 ± 3.8, and 128 ± 10.8 nMrespectively. 1-34 PTH had no effect. The various doses of PTH antagonist ([Tyr-34] bPTH (7-34)NH2) blocked the PTH-induced rise in [Ca2+]iby 41-67%. Dibutyryl adenosine 3’,5’-cyclic phosphatase (cAMP), forskolin and phorbol ester 12-0-tetradecanoyl-phorbol 13-acetate (TPA) also produced a significant rise in [Ca2+]iof thymocytes. Verapamil blocked the PTH action by 44% but had no effect on the dibutyryl-cAMP-, forskolin- or TPA-induced rise in [Ca2+]i. Absence of calcium in the media abolished the PTH-induced increase in [Ca2+]iand significantly reduced that of dibutyryl cAMP. Staurosprine completely prevented the TPA-induced rise in [Ca2+]ibut had no effect on that produced by PTH. 1-84 PTH in the presence of calcium in the medium produced a significant rise in thymocyte cAMP but had no effect in the absence of calcium in the media. The data indicate that (1) thymocytes are a target for PTH and that the intact hormones increased their [Ca2+]i, most likely, through a receptor-hormone interaction, (2) this action of the hormone appears to be partially mediated by its stimulation of cAMP generation and partially by activation of voltage-gated calcium channels, and (3) the rise in [Ca2+]iis, most likely due to both entry of calcium into the thymocytes and mobilization of calcium stores within the cells.