期刊
REGULATORY PEPTIDES
卷 109, 期 1-3, 页码 149-153出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/S0167-0115(02)00198-2
关键词
pituitary adenylate cyclase-activating polypeptide (PACAP); intracellular Ca2+ mobilization; Ca2+ influx; thapsigargin; phospholipase C; voltage-dependent calcium channel
We have recently shown that in PC12 cells, pituitary adenylate cyclase-activating polypeptide (PACAP) and NGF synergistically stimulate PACAP mRNA expression primarily via a mechanism involving a p38 mitogen-activated protein kinase (MAPK)-dependent pathway. Here we have analyzed p38 MAPK activation by PACAP and the mechanism underlying this action of PACAP in PC12 cells. PACAP increased phosphorylation of p38 MAPK with a bell-shaped dose-response relationship and a maximal effect was obtained at 10(-8) M. PACAP (10(-8) M)-induced p38 MAPK phosphorylation was already evident at 2.5 min, maximal at 5 min, and rapidly declined thereafter. PACAP-induced p38 MAPK phosphorylation was potently inhibited by depletion of Ca2+ stores with thapsigargin and partially inhibited by the phospholipase C inhibitor U-73122, L-type voltage-dependent calcium channel inhibitors nifedipine and nimodipine, and the Ca2+ chelator EGTA, whereas the protein kinase C inhibitor calphostin C, the protein kinase A inhibitor H-89, the cAMP antagonist Rp-cAMP, and the nonselective cation channel blocker SKF96365 had no effect. These results indicate that PACAP activates p38 MAPK in PC12 cells through activation of a phospholipase C, mobilization of intracellular Ca2+ stores, and Ca2+ influx through voltage-dependent Ca2+ channels, but not cyclic AMP-dependent mechanisms. (C) 2002 Elsevier Science B.V. All rights reserved.
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