Inositol trisphosphate, calcium and muscle contraction

Abstract

The identity of organelles storing intracellular calcium and the role of Ins(1,4,5)P3 in muscle have been explored with, respectively, electron probe X-ray microanalysis (EPMA) and laser photolysis of 'caged' compounds. The participation of G-protein(s) in the release of intracellular Ca2+ was determined in saponin-permeabilized smooth muscle. The sarcoplasmic reticulum (SR) is identified as the major source of activator Ca2+ in both smooth and striated muscle; similar (EPMA) studies suggest that the endoplasmic reticulum is the major Ca2+ storage site in non-muscle cells. In none of the cell types did mitochondria play a significant, physiological role in the regulation of cytoplasmic Ca2+. The latency of guinea pig portal vein smooth muscle contraction following photolytic release of phenylephrine, an alpha 1-agonist, is 1.5 +/- 0.26 s at 20 degrees C and 0.6 +/- 0.18 s at 30 degrees C; the latency of contraction after photolytic release of Ins(1,4,5)P3 from caged Ins(1,4,5)P3 is 0.5 +/- 0.12 s at 20 degrees C. The long latency of alpha 1-adrenergic Ca2+ release and its temperature dependence are consistent with a process mediated by G-protein-coupled activation of phosphatidylinositol 4,5 bisphosphate (PtdIns(4,5)P2) hydrolysis. GTP gamma S, a non-hydrolysable analogue of GTP, causes Ca2+ release and contraction in permeabilized smooth muscle. Ins(1,4,5)P3 has an additive effect during the late, but not the early, phase of GTP gamma S action, and GTP gamma S can cause Ca2+ release and contraction of permeabilized smooth muscles refractory to Ins(1,4,5)P3. These results suggest that activation of G protein(s) can release Ca2+ by, at least, two G-protein-regulated mechanisms: one mediated by Ins(1,4,5)P3 and the other Ins(1,4,5)P3-independent. The low Ins(1,4,5)P3 5-phosphatase activity and the slow time-course (seconds) of the contractile response to Ins(1,4,5)P3 released with laser flash photolysis from caged Ins(1,4,5)P3 in frog skeletal muscle suggest that Ins(1,4,5)P3 is unlikely to be the physiological messenger of excitation-contraction coupling of striated muscle. In contrast, in smooth muscle the high Ins(1,4,5)P3-5-phosphatase activity and the rate of force development after photolytic release of Ins(1,4,5)P3 are compatible with a physiological role of Ins(1,4,5)P3 as a messenger of pharmacomechanical coupling.

Des‐Arg9‐bradykinin‐induced increases in intracellular calcium ion concentration in single bovine tracheal smooth muscle cells

“…Bradykinin has been shown to elicit an increase in intracellular calcium ion concentration ([Ca2+],) of human (Murray & Kotlikoff, 1991) and guinea-pig (Farmer et al, 1991a,b) airway smooth muscle cells although the characteristics of these responses remain unclear. An increase in [Ca2J]i is a mechanism necessary for the contraction of smooth muscle and can be mediated either via an influx of calcium ions from the extracellular space (Benham & Tsien, 1987;Murray & Kotlikoff, 1991) or via a release of calcium from the intracellular stores which may result from an increase in production of inositol 1,4,5-trisphosphate (Somlyo et al, 1988;Berridge & Irvine, 1989).…”

Guanine nucleotide‐ and inositol 1,4,5‐trisphosphate‐induced calcium release in rabbit main pulmonary artery.

“…Our (Kobayashi, Somlyo & Somlyo, 1987 and to the Royal Society of London (Somlyo, Walker, Goldman, Trentham, Kobayashi, Kitazawa & Somlyo, 1988).…”

Kinetics of Prephosphorylation Reactions and Myosin Light Chain Phosphorylation in Smooth Muscle

“…A long lag phase between the binding of an excitatory agonist to its receptor and contraction is a characteristic property of smooth muscle, evident even when diffusional delays are eliminated through photolysis of caged agonists (Somlyo et al, 1988a;Muralidharan et al, 1993;Walker et al, 1993). A major component of the delay (1-2 s in guinea pig portal vein smooth muscle stimulated with phenylephrine at room temperature; Somlyo et al (1988a)) is due to phospholipase C-mediated generation of inositol 1,4,5-trisphosphate that is the messenger of pharmacomechanical Ca 2ϩ release from the sarcoplasmic reticulum (reviewed by Somlyo and Somlyo (1990)).…”