A role for inositol 145-trisphosphate in the initiation of agonist-induced contractions of dog tracheal smooth muscle.

摘要

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.(ABSTRACT TRUNCATED AT 250 WORDS)