Youdim M B
Technion-Bruce Rappaport Faculty of Medicine, Department of Pharmacology, Haifa, Israel.
J Neural Transm Suppl. 1991;34:61-7. doi: 10.1007/978-3-7091-9175-0_8.
Studies on PC12 and isolated adrenal chromaffin cells have revealed that PC12 cells have a closer identity to the adrenergic nerve ending than do the chromaffin cells. This is revealed by the presence of monoamine oxidase (MAO) A and tyramine-released pool of catecholamines in PC12, resembling that in adrenergic neurones, and their absence in adrenal chromaffin cells. Indeed, chromaffin cells possess primarily MAO-B activity. Like the observations on adrenergic neurones, non-selective and selective MAO-A inhibitors potentiate the catecholamine-releasing property of tyramine in PC12 cells. This property has clearly been demonstrated to be associated with selective inhibition of MAO-A and not MAO-B. The fact that MAO-A and MAO-B are different proteins and under separate gene product control suggests that their regulation may be highly differentiated. Indeed, it has been shown that while steroids such as progesterone and hydrocortisone induce and estrogen diminishes MAO-A activity in PC12 cells, no such regulatory mechanism has been identified for MAO-B activity in chromaffin cells. In the final analysis the inter-relationship between MAO-A activity and the presence of tyramine-releasable pool of catecholamines in adrenergic neurons and PC12 cells may have a genetic basis and could be important in illuminating the differentiation of neural crest into adrenergic neurones and adrenal medulla on the one hand and chromaffin cells to PC12 cells on the other.
对PC12细胞和分离的肾上腺嗜铬细胞的研究表明,与嗜铬细胞相比,PC12细胞与肾上腺素能神经末梢的特性更为相似。这体现在PC12细胞中存在单胺氧化酶(MAO)A和可释放酪胺的儿茶酚胺池,类似于肾上腺素能神经元中的情况,而肾上腺嗜铬细胞中则不存在。实际上,嗜铬细胞主要具有MAO - B活性。与对肾上腺素能神经元的观察结果一样,非选择性和选择性MAO - A抑制剂可增强酪胺在PC12细胞中释放儿茶酚胺的特性。这一特性已明确被证明与选择性抑制MAO - A而非MAO - B有关。MAO - A和MAO - B是不同的蛋白质且受不同基因产物控制,这一事实表明它们的调节可能高度分化。确实,已表明诸如孕酮和氢化可的松等类固醇可诱导PC12细胞中的MAO - A活性,而雌激素则会使其降低,然而尚未发现针对嗜铬细胞中MAO - B活性的此类调节机制。归根结底,MAO - A活性与肾上腺素能神经元及PC12细胞中可释放酪胺的儿茶酚胺池之间的相互关系可能具有遗传基础,并且一方面对于阐明神经嵴向肾上腺素能神经元和肾上腺髓质的分化,另一方面对于嗜铬细胞向PC12细胞的分化可能具有重要意义。