A role for inositol 1,4,5-trisphosphate in the initiation of agonist-induced contractions of dog tracheal smooth muscle.
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 X 10(-7) or 5 X 10(-5)M, respectively. The ATP-dependent Ca2+ accumulation was maximal at 0.63 nmol/10(5) cells. Effects of Ins-P3 on stored Ca2+ were observed at a free Ca2+ concentration of 3.7 X 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 microM 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 10s after this application, the relative amount of Ins-P3 was 290% of the control value. 6 Concomitantly, ACh (10- 5 M) either reduced or increased the contents ofphosphatidyl inositol 4,5-biphosphate (PI-P2) or phosphatidic acid (PA) in the lipid fraction ofthe smooth muscle cells to 60% or to 350% of the control value, respectively, thereby indicating that ACh stimulates the phosphodiesteric hydrolysis of PI-P2. 7 5-Hydroxytryptamine (5-HT; 10- 5M) also reduced or increased the contents of PI-P2 or PA to 80 or to 200% of the control values, respectively. However, neither histamine (10-5M), in the presence or absence of cimetidine (10-5M), nor prostaglandin F2 alpha. (PGF2 alpha. 1O-7 M) showed any effect on the contents of PI-P2 or PA in the lipid fraction of the smooth muscle cells. 8 These results indicate that in muscle cells of the dog trachea, Ins-P3 may play the role ofintracellular second messenger in the initiation of ACh or 5-HT-induced contraction, but not in the case of histamine or PGF2 alpha-induced contraction.
D006916:5-Hydroxytryptophan / Q000494:pharmacology; D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002927:Cimetidine / Q000494:pharmacology; D015237:Dinoprost; D004285:Dogs; D005260:Female; D006632:Histamine / Q000494:pharmacology; D066298:In Vitro Techniques; D015544:Inositol 1,4,5-Trisphosphate; D007295:Inositol Phosphates / Q000494:pharmacology*; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects*; D010712:Phosphatidic Acids / Q000378:metabolism; D011460:Prostaglandins F / Q000494:pharmacology; D012503:Saponins / Q000494:pharmacology; D013403:Sugar Phosphates / Q000494:pharmacology*; D013997:Time Factors; D014132:Trachea / Q000187:drug effects
D007295:Inositol Phosphates; D010712:Phosphatidic Acids; D011460:Prostaglandins F; D012503:Saponins; D013403:Sugar Phosphates; D002927:Cimetidine; D006632:Histamine; D015544:Inositol 1,4,5-Trisphosphate; D015237:Dinoprost; D006916:5-Hydroxytryptophan; D000109:Acetylcholine; D002118:Calcium