Holt E H, Broadus A E, Brines M L
Department of Cellular and Molecular Physiology, Yale University School of Medicine, New Haven, Connecticut 06520-8020, USA.
J Biol Chem. 1996 Nov 8;271(45):28105-11. doi: 10.1074/jbc.271.45.28105.
Parathyroid hormone (PTH)-related peptide (PTHrP) is expressed in the adult mammalian brain, but its function is unknown. Here we show that PTHrP and the PTH/PTHrP receptor are products of cerebellar granule cells in primary culture. Granule cells maintained under depolarizing conditions (25 mM K+) make and release PTHrP. Further, PTHrP-(1-36) stimulates cAMP accumulation in granule neurons in a dose-dependent manner with half-maximal activation at approximately 16 nM. Granule cell PTHrP mRNA is activity-dependent, and the pathway of regulation depends absolutely on the flux of Ca2+ ions through the L-type voltage-sensitive Ca2+ channel and the Ca2+/calmodulin kinase cascade. PTHrP is therefore a neuropeptide whose regulation depends upon L-type voltage-sensitive Ca2+ channel activity, and the gene is expressed under conditions that promote granule cell survival.
甲状旁腺激素相关肽（PTHrP）在成年哺乳动物大脑中表达，但其功能尚不清楚。在此我们表明，PTHrP和PTH/PTHrP受体是原代培养的小脑颗粒细胞的产物。在去极化条件（25 mM K+）下培养的颗粒细胞产生并释放PTHrP。此外，PTHrP-(1-36)以剂量依赖方式刺激颗粒神经元中的cAMP积累，在约16 nM时达到半数最大激活。颗粒细胞PTHrP mRNA具有活性依赖性，其调节途径绝对依赖于Ca2+离子通过L型电压敏感性Ca2+通道的通量以及Ca2+/钙调蛋白激酶级联反应。因此，PTHrP是一种神经肽，其调节依赖于L型电压敏感性Ca2+通道活性，并且该基因在促进颗粒细胞存活的条件下表达。
