Abstract:
:Platelet-derived growth factor (PDGF) stimulates cyclic AMP (cAMP) synthesis in cultured guinea-pig airway smooth muscle (ASM) cells. However, this stimulation is normally countered by the action of cAMP phosphodiesterases. Thus, cAMP synthesis was observed only in cells pre-treated with either 3-isobutyl-1-methylxanthine (IBMX) or with cholera toxin. cAMP synthesis was inhibited by pre-treating cells with well-defined inhibitors of arachidonate metabolite synthesis, such as AACOCF3 [a cytosolic phospholipase A2 (cPLA2) inhibitor] and indomethacin (a cyclooxygenase inhibitor). This suggests that arachidonate metabolites (e.g., prostaglandins) released in response to PDGF stimulate cAMP synthesis. The presence of functional prostaglandin (PG) receptors was confirmed by experiments that showed that exogenous PGE2 stimulated cAMP formation. cPLA2 is regulated by mitogen-activated protein kinase (MAPK) in a number of cell types. The presence of this pathway in ASM cells and its role in regulating arachidonate metabolism were supported by the finding that pre-treatment of cells with PD098059 (an inhibitor of mitogen-activated protein kinase kinase-1 activation) reduced PDGF-stimulated cAMP synthesis. The cAMP formed in response to the arachidonate metabolites subsequently reduced the PDGF-dependent activation of c-Raf, MAPK, and DNA synthesis, suggesting the presence of a negative feedback pathway.
journal_name
Cell Signaljournal_title
Cellular signallingauthors
Pyne NJ,Pyne Sdoi
10.1016/s0898-6568(97)00138-1subject
Has Abstractpub_date
1998-05-01 00:00:00pages
363-9issue
5eissn
0898-6568issn
1873-3913pii
S0898-6568(97)00138-1journal_volume
10pub_type
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journal_title:Cellular signalling
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doi:10.1016/j.cellsig.2008.05.011
更新日期:2009-03-27 00:00:00
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pub_type: 杂志文章,评审
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journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/s0898-6568(01)00247-9
更新日期:2002-02-01 00:00:00
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journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/s0898-6568(97)00036-3
更新日期:1998-03-01 00:00:00
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journal_title:Cellular signalling
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journal_title:Cellular signalling
pub_type: 杂志文章
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journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/0898-6568(89)90057-0
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journal_title:Cellular signalling
pub_type: 杂志文章
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journal_title:Cellular signalling
pub_type: 杂志文章
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journal_title:Cellular signalling
pub_type: 杂志文章
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更新日期:1995-05-01 00:00:00
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journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/0898-6568(93)90038-n
更新日期:1993-11-01 00:00:00
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journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/j.cellsig.2009.01.037
更新日期:2009-06-01 00:00:00
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journal_title:Cellular signalling
pub_type: 杂志文章,评审
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更新日期:1996-11-01 00:00:00
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journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/j.cellsig.2017.10.017
更新日期:2018-01-01 00:00:00
abstract::Whole-cell currents activated by bath applications of acetylcholine (ACh) (10-30 microM) were recorded from patch-clamped myotubes of the mouse C2 cell line. Increasing concentrations of forskolin caused a dose-dependent fast decay of ACh-activated currents as compared to the long-lasting ACh-currents in control cells...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/0898-6568(90)90064-h
更新日期:1990-01-01 00:00:00