Schmidt M, Löffler G
Institut für Biochemie, Genetik und Mikrobiologie, Universität Regensburg, Germany.
Eur J Biochem. 1998 Feb 15;252(1):147-54. doi: 10.1046/j.1432-1327.1998.2520147.x.
Here we describe properties of the P2-purinoceptor, which is involved in the regulation of the key enzyme of estrogen biosynthesis, aromatase cytochrome P-450, in stromal cells from human adipose tissue. Aromatase activity induced by cortisol and platelet-derived growth factor BB (PDGF-BB) is further increased by addition of ATP, ADP, AMP and, albeit with reduced potency, adenosine, GTP and adenosine(5')tetraphospho(5') adenosine. Stable P1-purinoceptor agonists are inactive, whereas P2X-purinoceptor agonists mimic the effects of purine(s) (nucleotides). Prior incubation of cells with a P2-purinoceptor antagonist, but not P1-purinoceptor antagonists, blocks augmentation of aromatase activity by all ligands. Nucleotides, but not adenosine, retain their ability to augment aromatase activity in the presence of adenosine deaminase, indicating that they do not act via their metabolite adenosine. These results lead to the conclusion, that at least one member of the P2-subclass of purinoceptors exists in adipose tissue and is involved in modulation of aromatase activity in vitro. The pharmacological profile of the P2-site differs from those reported for cloned P2-purinoceptors, but is similar to that of the P2X-subclass. Therefore, a combined response of different members of the P2X-purinoceptor subclass or of members of different P2-purinoceptor subclasses cannot be discounted. Purinoceptor activation triggers cytoplasmic calcium transients, which, in contrast to aromatase induction, are independent from the presence of cortisol and PDGF-BB. Therefore the involved P2-purinoceptor(s) seem(s) to be constitutively expressed in human adipose tissue stromal cells. P2-purinoceptor(s) might provide a direct link between sympathetic nerve activity and estrogen biosynthesis in human adipose tissue. Furthermore it (or they) may contribute to the regulation of lipolysis.
在此，我们描述了P2 - 嘌呤受体的特性，该受体参与调节人脂肪组织基质细胞中雌激素生物合成的关键酶——芳香化酶细胞色素P - 450。皮质醇和血小板衍生生长因子BB（PDGF - BB）诱导的芳香化酶活性，在添加ATP、ADP、AMP以及（尽管效力较低）腺苷、GTP和腺苷 - 5'-四磷酸 - 5'-腺苷后会进一步增强。稳定的P1 - 嘌呤受体激动剂无活性，而P2X - 嘌呤受体激动剂可模拟嘌呤（核苷酸）的作用。用P2 - 嘌呤受体拮抗剂而非P1 - 嘌呤受体拮抗剂预先孵育细胞，可阻断所有配体对芳香化酶活性的增强作用。在腺苷脱氨酶存在的情况下，核苷酸而非腺苷仍保留其增强芳香化酶活性的能力，这表明它们并非通过其代谢产物腺苷发挥作用。这些结果得出结论，脂肪组织中存在嘌呤受体P2 - 亚类的至少一个成员，且在体外参与芳香化酶活性的调节。P2位点的药理学特征与报道的克隆P2 - 嘌呤受体不同，但与P2X - 亚类相似。因此，不能排除P2X - 嘌呤受体亚类的不同成员或不同P2 - 嘌呤受体亚类的成员的联合反应。嘌呤受体激活引发细胞质钙瞬变，与芳香化酶诱导不同的是，其独立于皮质醇和PDGF - BB的存在。因此，所涉及的P2 - 嘌呤受体似乎在人脂肪组织基质细胞中组成性表达。P2 - 嘌呤受体可能为人脂肪组织中交感神经活动与雌激素生物合成之间提供直接联系。此外，它（或它们）可能有助于脂肪分解的调节。
