Cheng L, Khan M, Mudge A W
Medical Research Council Laboratory for Molecular Cell Biology, University College London, United Kingdom.
J Cell Biol. 1995 May;129(3):789-96. doi: 10.1083/jcb.129.3.789.
Schwann cells in culture divide in response to defined mitogens such as PDGF and glial growth factor (GGF), but proliferation is greatly enhanced if agents such as forskolin, which increases Schwann cell intracellular cAMP, are added at the same time as PDGF or GGF (Davis, J. B., and P. Stroobant. 1990. J. Cell Biol. 110:1353-1360). The effect of forskolin is probably due to an increase in numbers of PDGF receptors (Weinmaster, G., and G. Lemke. 1990. EMBO (Eur. Mol. Biol. Organ.) J. 9:915-920. Neuropeptides and beta-adrenergic agonists have been reported to have no effect on potentiating the mitogenic response of either PDGF or GGF. We show that the neuropeptide calcitonin gene-related peptide (CGRP) increases Schwann cell cAMP levels, but the cells rapidly desensitize. We therefore stimulated the cells in pulsatile fashion to partly overcome the effects of desensitization and show that CGRP can synergize with PDGF to stimulate Schwann cell proliferation, and that CGRP is as effective as forskolin in the pulsatile regime. CGRP is a good substrate for the neutral endopeptidase 24.11. Schwann cells in vivo have this protease on their surface, so the action of CGRP could be terminated by this enzyme and desensitization prevented. We therefore suggest that CGRP may play an important role in stimulating Schwann cell proliferation by regulating the response of mitogenic factors such as PDGF.
培养中的施万细胞会对特定的促有丝分裂原如血小板衍生生长因子（PDGF）和神经胶质生长因子（GGF）作出反应而分裂，但如果在添加PDGF或GGF的同时加入能增加施万细胞细胞内cAMP的药物如福斯高林，增殖会显著增强（戴维斯，J.B.，和P.斯特鲁班特。1990。《细胞生物学杂志》110:1353 - 1360）。福斯高林的作用可能是由于PDGF受体数量的增加（温马斯特，G.，和G.莱姆克。1990。《欧洲分子生物学组织杂志》9:915 - 920）。据报道，神经肽和β - 肾上腺素能激动剂对增强PDGF或GGF的促有丝分裂反应没有作用。我们发现神经肽降钙素基因相关肽（CGRP）能增加施万细胞的cAMP水平，但细胞会迅速脱敏。因此，我们以脉冲方式刺激细胞以部分克服脱敏效应，并表明CGRP能与PDGF协同刺激施万细胞增殖，且在脉冲模式下CGRP与福斯高林的效果相同。CGRP是中性内肽酶24.11的良好底物。体内的施万细胞表面有这种蛋白酶，所以CGRP的作用可能会被这种酶终止，从而防止脱敏。因此，我们认为CGRP可能通过调节诸如PDGF等促有丝分裂因子的反应在刺激施万细胞增殖中发挥重要作用。
