Waschek J A, Eiden L E
Laboratory of Cell Biology, National Institute of Mental Health, Bethesda, MD 20892.
Neuropeptides. 1988 Jan;11(1):39-45. doi: 10.1016/0143-4179(88)90026-1.
The divalent cation barium was used to study the role of calcium in coupling neuropeptide secretion and biosynthesis following secretagogue stimulation of bovine chromaffin cells. Barium chloride (0.1-2.5 mM) stimulated in a dose-dependent manner the secretion of met-enkephalin (up to 20% of intracellular peptide content) and increased the total amount (cell plus medium content) of met-enkephalin and vasoactive intestinal polypeptide (VIP) 2- to 3-fold after 72 hours. A greater than six-fold increase in proenkephalin mRNA (mRNA(enk)) was observed by 24 hours following barium stimulation. The voltage-sensitive calcium channel blocker D600 inhibited the barium-stimulated secretion of enkephalin and blocked the stimulation of VIP biosynthesis and mRNA(enk). Reducing calcium in the medium resulted in an enhancement of barium-stimulated release of both peptides, but blocked the induction of their biosynthesis. The data indicate that calcium targets involved in secretion can be activated by barium or calcium while calcium targets involved in biosynthesis specifically require calcium. It is therefore proposed that pathways leading to peptide secretion and biosynthesis in the adrenal diverge just after secretagogue-stimulated calcium influx.
使用二价阳离子钡来研究钙在促分泌素刺激牛嗜铬细胞后耦联神经肽分泌与生物合成过程中的作用。氯化钡（0.1 - 2.5 mM）以剂量依赖性方式刺激甲硫氨酸脑啡肽的分泌（高达细胞内肽含量的20%），并在72小时后使甲硫氨酸脑啡肽和血管活性肠肽（VIP）的总量（细胞加培养基中的含量）增加2至3倍。钡刺激后24小时，前脑啡肽mRNA（mRNA(enk)）增加超过6倍。电压敏感性钙通道阻滞剂D600抑制钡刺激的脑啡肽分泌，并阻断对VIP生物合成和mRNA(enk)的刺激。降低培养基中的钙会增强钡刺激的两种肽的释放，但会阻断它们生物合成的诱导。数据表明，参与分泌的钙靶点可被钡或钙激活，而参与生物合成的钙靶点则特别需要钙。因此，有人提出，在促分泌素刺激钙内流后，肾上腺中导致肽分泌和生物合成的途径就会分开。
