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A role for inositol 1,4,5‐trisphosphate in the initiation of agonist‐induced contractions of dog tracheal smooth muscle
Author(s) -
Hashimoto Toshihiko,
Hirata Masato,
Ito Yushi
Publication year - 1985
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1985.tb09449.x
Subject(s) - inositol , phosphatidic acid , phosphatidylinositol , chemistry , acetylcholine , medicine , contraction (grammar) , endocrinology , muscle contraction , agonist , inositol trisphosphate , myocyte , inositol phosphate , biology , receptor , biochemistry , signal transduction , phospholipid , membrane
1 To elucidate the role of inositol 1,4,5‐trisphosphate (Ins‐P 3 ) in the initiation of agonist‐induced contraction of the smooth muscle cells of the dog trachea, we investigated the effects of acetylcholine (ACh) on the concentrations of Ins‐P 3 , phosphatidylinositol‐4,5‐bisphosphate (PI‐P 2 ) or phosphatidic acid (PA). The effects of Ins‐P 3 on the Ca 2+ stored in the smooth muscle cells were also studied in saponin‐permeabilized smooth muscle cells. 2 A half maximal or maximal Ca 2+ accumulation into the cells was observed in the dispersed single, smooth muscle cells treated by saponin, in free Ca 2+ concentrations of 4.6 × 10 −7 or 5 × 10 −5 M, respectively. The ATP‐dependent Ca 2+ accumulation was maximal at 0.63 nmol/10 5 cells. 3 Effects of Ins‐P 3 on stored Ca 2+ were observed at a free Ca 2+ concentration of 3.7 × 10 −7 M, which induces about half maximal ATP‐dependent Ca 2+ ‐accumulation. Ins‐P 3 released the Ca 2+ accumulated by ATP, in a dose‐dependent manner. About 40% of the total Ca 2+ was released following application of 3 μM Ins‐P 3 . 4 The release of stored Ca 2+ induced by application of Ins‐P 3 was followed by its re‐uptake into the smooth muscle cells. Thus, the stored Ca 2+ was repeatedly released with repetitive applications of Ins‐P 3 . 5 Application of ACh (10 −5 M) to the dog trachea stimulated the production of Ins‐P 3 in the soluble fraction and 10 s after this application, the relative amount of Ins‐P 3 was 290% of the control value. 6 Concomitantly, ACh (10 −5 M) either reduced or increased the contents of phosphatidyl inositol 4,5‐biphosphate (PI‐P 2 ) or phosphatidic acid (PA) in the lipid fraction of the smooth muscle cells to 60% or to 350% of the control value, respectively, thereby indicating that ACh stimulates the phosphodiesteric hydrolysis of PI‐P 2 . 7 5‐Hydroxytryptamine (5‐HT; 10 −5 M) also reduced or increased the contents of PI‐P 2 or PA to 80 or to 200% of the control values, respectively. However, neither histamine (10 −5 M), in the presence or absence of cimetidine (10 −5 M), nor prostaglandin F 2α (PGF 2α 10 −7 M) showed any effect on the contents of PI‐P 2 or PA in the lipid fraction of the smooth muscle cells. 8 These results indicate that in muscle cells of the dog trachea, Ins‐P 3 may play the role of intracellular second messenger in the initiation of ACh or 5‐HT‐induced contraction, but not in the case of histamine or PGF 2α ‐induced contraction.