A role for inositol 1,4,5‐trisphosphate in the initiation of agonist‐induced contractions of dog tracheal smooth muscle

Toshihiko Hashimoto, Masato Hirata, Yushi Ito

Research output: Contribution to journalArticle

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Abstract

To elucidate the role of inositol 1,4,5‐trisphosphate (Ins‐P3) 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‐P3, phosphatidylinositol‐4,5‐bisphosphate (PI‐P2) or phosphatidic acid (PA). The effects of Ins‐P3 on the Ca2+ stored in the smooth muscle cells were also studied in saponin‐permeabilized smooth muscle cells. A half maximal or maximal Ca2+ accumulation into the cells was observed in the dispersed single, smooth muscle cells treated by saponin, in free Ca2+ concentrations of 4.6 × 10−7 or 5 × 10−5 M, respectively. The ATP‐dependent Ca2+ accumulation was maximal at 0.63 nmol/105 cells. Effects of Ins‐P3 on stored Ca2+ were observed at a free Ca2+ concentration of 3.7 × 10−7 M, which induces about half maximal ATP‐dependent Ca2+‐accumulation. Ins‐P3 released the Ca2+ accumulated by ATP, in a dose‐dependent manner. About 40% of the total Ca2+ was released following application of 3 μM Ins‐P3. The release of stored Ca2+ induced by application of Ins‐P3 was followed by its re‐uptake into the smooth muscle cells. Thus, the stored Ca2+ was repeatedly released with repetitive applications of Ins‐P3. Application of ACh (10−5 M) to the dog trachea stimulated the production of Ins‐P3 in the soluble fraction and 10 s after this application, the relative amount of Ins‐P3 was 290% of the control value. Concomitantly, ACh (10−5 M) either reduced or increased the contents of phosphatidyl inositol 4,5‐biphosphate (PI‐P2) 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‐P2. 5‐Hydroxytryptamine (5‐HT; 10−5 M) also reduced or increased the contents of PI‐P2 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 (PGF 10−7 M) showed any effect on the contents of PI‐P2 or PA in the lipid fraction of the smooth muscle cells. These results indicate that in muscle cells of the dog trachea, Ins‐P3 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‐induced contraction. 1985 British Pharmacological Society

Original languageEnglish
Pages (from-to)191-199
Number of pages9
JournalBritish Journal of Pharmacology
Volume86
Issue number1
DOIs
Publication statusPublished - Jan 1 1985

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Inositol
Smooth Muscle Myocytes
Smooth Muscle
Dogs
Phosphatidic Acids
Acetylcholine
Trachea
Dinoprost
Histamine
Lipids
Cimetidine
Saponins
Second Messenger Systems
Phosphatidylinositols
Muscle Cells
Hydrolysis
Adenosine Triphosphate

All Science Journal Classification (ASJC) codes

  • Pharmacology

Cite this

A role for inositol 1,4,5‐trisphosphate in the initiation of agonist‐induced contractions of dog tracheal smooth muscle. / Hashimoto, Toshihiko; Hirata, Masato; Ito, Yushi.

In: British Journal of Pharmacology, Vol. 86, No. 1, 01.01.1985, p. 191-199.

Research output: Contribution to journalArticle

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N2 - To elucidate the role of inositol 1,4,5‐trisphosphate (Ins‐P3) 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‐P3, phosphatidylinositol‐4,5‐bisphosphate (PI‐P2) or phosphatidic acid (PA). The effects of Ins‐P3 on the Ca2+ stored in the smooth muscle cells were also studied in saponin‐permeabilized smooth muscle cells. A half maximal or maximal Ca2+ accumulation into the cells was observed in the dispersed single, smooth muscle cells treated by saponin, in free Ca2+ concentrations of 4.6 × 10−7 or 5 × 10−5 M, respectively. The ATP‐dependent Ca2+ accumulation was maximal at 0.63 nmol/105 cells. Effects of Ins‐P3 on stored Ca2+ were observed at a free Ca2+ concentration of 3.7 × 10−7 M, which induces about half maximal ATP‐dependent Ca2+‐accumulation. Ins‐P3 released the Ca2+ accumulated by ATP, in a dose‐dependent manner. About 40% of the total Ca2+ was released following application of 3 μM Ins‐P3. The release of stored Ca2+ induced by application of Ins‐P3 was followed by its re‐uptake into the smooth muscle cells. Thus, the stored Ca2+ was repeatedly released with repetitive applications of Ins‐P3. Application of ACh (10−5 M) to the dog trachea stimulated the production of Ins‐P3 in the soluble fraction and 10 s after this application, the relative amount of Ins‐P3 was 290% of the control value. Concomitantly, ACh (10−5 M) either reduced or increased the contents of phosphatidyl inositol 4,5‐biphosphate (PI‐P2) 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‐P2. 5‐Hydroxytryptamine (5‐HT; 10−5 M) also reduced or increased the contents of PI‐P2 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 F2α (PGF2α 10−7 M) showed any effect on the contents of PI‐P2 or PA in the lipid fraction of the smooth muscle cells. These results indicate that in muscle cells of the dog trachea, Ins‐P3 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 PGF2α‐induced contraction. 1985 British Pharmacological Society

AB - To elucidate the role of inositol 1,4,5‐trisphosphate (Ins‐P3) 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‐P3, phosphatidylinositol‐4,5‐bisphosphate (PI‐P2) or phosphatidic acid (PA). The effects of Ins‐P3 on the Ca2+ stored in the smooth muscle cells were also studied in saponin‐permeabilized smooth muscle cells. A half maximal or maximal Ca2+ accumulation into the cells was observed in the dispersed single, smooth muscle cells treated by saponin, in free Ca2+ concentrations of 4.6 × 10−7 or 5 × 10−5 M, respectively. The ATP‐dependent Ca2+ accumulation was maximal at 0.63 nmol/105 cells. Effects of Ins‐P3 on stored Ca2+ were observed at a free Ca2+ concentration of 3.7 × 10−7 M, which induces about half maximal ATP‐dependent Ca2+‐accumulation. Ins‐P3 released the Ca2+ accumulated by ATP, in a dose‐dependent manner. About 40% of the total Ca2+ was released following application of 3 μM Ins‐P3. The release of stored Ca2+ induced by application of Ins‐P3 was followed by its re‐uptake into the smooth muscle cells. Thus, the stored Ca2+ was repeatedly released with repetitive applications of Ins‐P3. Application of ACh (10−5 M) to the dog trachea stimulated the production of Ins‐P3 in the soluble fraction and 10 s after this application, the relative amount of Ins‐P3 was 290% of the control value. Concomitantly, ACh (10−5 M) either reduced or increased the contents of phosphatidyl inositol 4,5‐biphosphate (PI‐P2) 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‐P2. 5‐Hydroxytryptamine (5‐HT; 10−5 M) also reduced or increased the contents of PI‐P2 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 F2α (PGF2α 10−7 M) showed any effect on the contents of PI‐P2 or PA in the lipid fraction of the smooth muscle cells. These results indicate that in muscle cells of the dog trachea, Ins‐P3 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 PGF2α‐induced contraction. 1985 British Pharmacological Society

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