Fetal alveolar epithelial cells contain [D-Ala(2)]-deltorphin I-like immunoreactivity: delta- and mu-opiate receptors mediate opposite effects in developing lung.
Fetal alveolar epithelial cells contain [D-Ala(2)]-deltorphin I-like immunoreactivity: delta- and mu-opiate receptors mediate opposite effects in developing lung.
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胎儿肺泡上皮细胞含有 [D-Ala(2)]-deltorphin I 样免疫反应性：δ- 和 mu-阿片受体在发育中的肺中介导相反的作用。
DOI：
10.1165/ajrcmb.25.4.4072
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发表时间：
2001
期刊：
影响因子：
--
通讯作者：
Erspamer,V
中科院分区：
文献类型：
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作者：
Sunday,ME;Haley,KJ;Emanuel,RL;Torday,JS;Asokananthan,N;Sikorski,KA;Tooyama,I;Kimura,H;Renda,T;Erspamer,V
阿片样肽可以调节许多细胞功能。我们现在定位[D-Ala(2)]Deltorphin I(DADTI)样免疫反应(DADTI-LI)在发育中的小鼠肺，并分析潜在的功能作用。DADTI-LI阳性细胞多为前表面活性蛋白(ProSP)-C免疫反应阴性的肺泡细胞。DADTI-LI阳性细胞数高峰出现在胚胎第18天，出生后逐渐减少。为了分析DADTI对E17-18肺外植体发育的影响，用[D-Ala(2)]Deltorphin II(DADTII，可溶性DADTI类似物，Delta受体专一性)和地吗啡(Mu受体专一性)处理E17-18肺外植体。通过[(3)H]胆碱掺入饱和磷脂酰胆碱和ProSP-C免疫组织化学染色检测，DADTII抑制II型肺泡细胞分化，而DADTII则刺激DADTII促进II型肺泡细胞分化。[(3)H]-胸腺嘧啶核苷掺入和增殖细胞核抗原免疫染色检测细胞增殖，DADTII刺激细胞增殖，去甲吗啡抑制细胞增殖。所有效应均呈剂量依赖关系。DADTII抑制的胆碱掺入可被增量阻滞剂纳曲哚逆转。出乎意料的是，DADTII刺激的胸腺嘧啶核苷掺入被纳曲多增强，并被MU阻滞剂纳洛酮逆转。尽管去甲吗啡刺激的胆碱掺入可被联苯乙胺适当阻断，但去吗啡抑制的胸腺嘧啶核苷掺入可被Delta、Kappa或Mu受体阻滞剂逆转。Delta和Mu受体信使RNA在出生前和出生后发生，而kappa受体转录本主要在产前发生。三种受体蛋白均表达于E18肺上皮细胞和间充质细胞。因此，来自ProSP-C免疫阴性肺泡细胞的DADTI-LI可以通过涉及多个阿片受体的直接和间接作用来调节发育。
Opiate-like peptides can regulate many cellular functions. We now map [D-Ala (2)] deltorphin I (DADTI)-like immunoreactivity (DADTI-LI) in developing mouse lung and analyze potential functional roles. Most DADTI-LI-positive cells were alveolar cells negative for prosurfactant protein (proSP)-C immunoreactivity. Peak numbers of DADTI-LI-positive cells occurred on embryonic Day 18, decreasing postnatally. To analyze developmental effects of DADTI, e17-18 lung explants were treated with [D-Ala (2)] deltorphin II (DADTII, soluble DADTI analogue, delta-receptor-specific) versus dermorphin (mu-receptor-specific). Type II pneumocyte differentiation, assessed by [(3) H] choline incorporation into saturated phosphatidylcholine and proSP-C immunostaining, was inhibited by DADTII but stimulated by dermorphin. Cell proliferation, measured as [(3) H]-thymidine incorporation and proliferating cell nuclear antigen immunostaining, was stimulated by DADTII and inhibited by dermorphin. All effects were dose-dependent. DADTII-inhibited choline incorporation was reversed by the delta-blocker, naltrindole. Unexpectedly, DADTII-stimulated thymidine incorporation was augmented by naltrindole and reversed by naloxone (mu-blocker). Although dermorphin-stimulated choline incorporation was appropriately blocked by binaltorphimine, dermorphin-inhibited thymidine incorporation was reversed by delta, kappa-, or mu-blockers. The delta-and mu-receptor messenger RNAs occurred pre-and postnatally, whereas kappa-receptor transcripts occurred mainly prenatally. All three receptor proteins were present in epithelial and mesenchymal cells in e18 lung. Thus, DADTI-LI from proSP-C-immunonegative alveolar cells could regulate development via both direct and indirect effects involving multiple opiate receptors.