Effect of forskolin on bradykinin-induced calcium mobilization in
tracheal muscle cells.
Luo, Shue-Fen, Chi-Tso Chiu, Hui-Liang Tsao, Richard Ong, Lir-Wan Fan,
Chuen-Tao Tsai, and Chuen-Mao Yang.
Department of Internal Medicine and Cellular and Molecular
Pharmacology Laboratory, Department of Pharmacology, Chang Gung
College of Medicine and Technology, Kwei-San, Tao-Yuan, Taiwan,
Republic of China
APStracts 3:0160C, 1996.
The effects of increases in intracellular adenosine 3':5'-cyclic
monophosphate (cyclic AMP) on bradykinin (BK)-induced generation of
inositol phosphates (IPs) and Ca2+ mobilization were investigated in
canine cultured tracheal smooth muscle cells (TSMCs). Cholera toxin
and forskolin induced concentration- and time-dependent cyclic AMP
formation. 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-7B-(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
KD and Bmax values of the BK receptor for [3H]BK binding were not
significantly changed by forskolin treatment for 30 min and 4 h. The
AlF4--induced IPs accumulation was attenuated by forskolin,
indicating that G protein(s) are directly activated by AlF4- 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 [Ca2+]i increases
or inhibit independently both responses, which is distal to the BK
receptor in canine cultured TSMCs.
Received 17 October 1995; accepted in final form 2 May 1996.
APS Manuscript Number C631-5.
Article publication pending Am. J. Physiol. (Cell Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 28 May 96