Effect of forskolin on bradykinin-induced calcium mobilization in cultured canine tracheal smooth muscle cells

Shue Fen Luo, Chi Tso Chiu, Hui Liang Tsao, Lir Wan Fan, Chuen Tao Tsai, Shiow Lin Pan, Chuen Mao Yang

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8 引文 斯高帕斯(Scopus)


The effects of increases in intracellular adenosine 3':5'-cyclic monophosphate (cyclic AMP) on bradykinin (BK)-induced generation of inositol phosphates (IPs) and Ca 2+ mobilization were investigated in canine cultured tracheal smooth muscle cells (TSMCs). Pretreatment of TSMCs with either forskolin or dibutyryl cyclic AMP attenuated BK-stimulated responses. The inhibitory effects of these agents produced both a depression of the maximal response and a shift to the right of the concentration-response curves of BK. The water-soluble forskolin analogue L-858051, 7-deacetyl-7β-(r-N-methylpiperazino)-butyryl forskolin, significantly attenuated BK-stimulated IPs accumulation, while 1,9-dideoxy forskolin, an inactive forskolin, had little effect on IPs response. Moreover, SQ-22536, 9-(tetrahydro-2-furanyl)-9-H-purin-6-amine, an inhibitor of adenylate cyclase, and both H-89, N-(2-aminoethyl)-5-isoquinolinesulfonamide and HA-1004, N-(2-guanidinoethyl)-5-isoquinolinesulfonamide, inhibitors of cyclic AMP dependent protein kinase (PKA), reversed the ability of forskolin to attenuate BK stimulated IPs accumulation. The K(D) and B(max) values of the BK receptor for [ 3H]BK binding were not significantly changed by forskolin treatment for 30 min and 4 h. The AIF 4 --induced IPs accumulation was attenuated by forskolin, indicating that G protein(s) are directly activated by AIF 4 - and uncoupled to phospholipase C by forskolin treatment. These results suggest that activation of cyclic AMP/PKA might inhibit the BK-stimulated PI breakdown and consequently reduce the [Ca 2+](i) increases or inhibit independently both responses, which is distal to the BK receptor in canine cultured TSMCs.
頁(從 - 到)159-167
期刊Cellular Signalling
出版狀態已發佈 - 2月 1997

ASJC Scopus subject areas

  • 細胞生物學


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