Petit A, Bélisle S
Department of Obstetrics and Gynecology, Université de Montréal, Hôpital Ste-Justine, Quebec, Canada.
J Clin Endocrinol Metab. 1995 Jun;80(6):1809-15. doi: 10.1210/jcem.80.6.7775628.
Recent data suggest an important role for calcium (Ca2+) in human placental endocrinology. Thus, the regulation of Ca2+ influx seems to be implicated in the modulation of human placental lactogen and hCG release. A possible mechanism of influx regulation is through receptor-operated channels. One of the most characterized receptor gating Ca2+ channels, the ATP receptor, stimulates the intracellular calcium concentration ([Ca2+]i) in various tissues. The aim of this study was to determine whether ATP receptors gating Ca2+ channels are also present in placental cells. We thus determined the effect of ATP on [Ca2+]i in human term trophoblastic cells loaded with the Ca(2+)-responsive fluorescent dye fura-2. ATP stimulated a 4.3 +/- 0.4 (+/- SE)-fold increase in [Ca2+]i, with a half-maximal effective concentration (EC50) of 1.5 mumol/L. The pharmacological activation profile suggests the presence of purinergic P2u receptors (nucleotide receptors), because uridine 5'-triphosphate (UTP) also stimulated [Ca2+]i (4.0-fold increase, with an EC50 of 10 mumol/L). The ATP-stimulated [Ca2+]i was partly sensitive to pertussis toxin; we observed a 58% inhibition of ATP-induced [Ca2+]i with the toxin without effect on basal [Ca2+]i. The ATP- and UTP-stimulated [Ca2+]i declined with time in the presence of ATP (or UTP). The rate of deactivation was rapid (t1/2, < 60 s with 10(-5) mol/L ATP) and concentration dependent. The deactivation occurring during one application of ATP or UTP resulted in a diminution of subsequent responses. The recovery was incomplete even with long waiting times (up to 30 min). ATP and UTP also stimulated inositol phosphate production with EC50 values of 11 and 15 mumol/L, respectively, but not human placental lactogen or hCG release in experiments in which known secretagogues were effective. The results suggest the presence in human term placental cells of P2u receptors pharmacologically similar to those observed in other tissues, especially in the pituitary and amnion. The physiological significance of this stimulation of [Ca2+]i by ATP and UTP in the human placenta remains to be investigated.
近期数据表明钙（Ca2+）在人胎盘内分泌学中发挥着重要作用。因此，Ca2+内流的调节似乎与人类胎盘催乳素和人绒毛膜促性腺激素（hCG）的释放调节有关。内流调节的一种可能机制是通过受体操纵通道。最具特征的受体门控Ca2+通道之一，即ATP受体，可刺激多种组织中的细胞内钙浓度（[Ca2+]i）。本研究的目的是确定胎盘细胞中是否也存在门控Ca2+通道的ATP受体。因此，我们测定了ATP对加载了Ca(2+)响应荧光染料fura-2的足月人滋养层细胞中[Ca2+]i的影响。ATP刺激[Ca2+]i增加了4.3±0.4（±SE）倍，半数有效浓度（EC50）为1.5μmol/L。药理学激活特征表明存在嘌呤能P2u受体（核苷酸受体），因为尿苷5'-三磷酸（UTP）也刺激了[Ca2+]i（增加4.0倍，EC50为10μmol/L）。ATP刺激的[Ca2+]i对百日咳毒素部分敏感；我们观察到毒素使ATP诱导的[Ca2+]i抑制了58%，而对基础[Ca2+]i无影响。在存在ATP（或UTP）的情况下，ATP和UTP刺激的[Ca2+]i随时间下降。失活速率很快（t1/2，10(-5)mol/L ATP时<60秒）且呈浓度依赖性。一次应用ATP或UTP期间发生的失活导致后续反应减弱。即使等待时间很长（长达30分钟），恢复也不完全。在已知促分泌剂有效的实验中，ATP和UTP还刺激了肌醇磷酸的产生，EC50值分别为11和15μmol/L，但未刺激人胎盘催乳素或hCG的释放。结果表明，足月人胎盘细胞中存在药理学上与其他组织（尤其是垂体和羊膜）中观察到的P2u受体相似的受体。ATP和UTP在人胎盘中刺激[Ca2+]i的生理意义仍有待研究。
