This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (11) Citing Articles via Google Scholar Google Scholar Articles by Kudoh, A. Articles by Matsuki, A. Search for Related Content PubMed PubMed Citation Articles by Kudoh, A. Articles by Matsuki, A.

---

GENERAL ARTICLES

Sevoflurane Stimulates Inositol 1,4,5-Trisphosphate in Skeletal Muscle

Department of Anesthesiology, University of Hirosaki School of Medicine, Hirosaki, Japan

Address correspondence and reprint requests to Akira Kudoh, MD, Department of Anesthesiology, University of Hirosaki School of Medicine, 5 Zaifucho, Hirosaki 036, Aomori, Japan.

Inositol 1,4,5-triphosphate (IP₃) plays an important role in excitation-contraction coupling and malignant hyperthermia in skeletal muscle. We investigated whether sevoflurane affects IP₃ formation in L₆ skeletal muscle cells and studied the mechanisms that modulate IP₃. Sevoflurane stimulated IP₃ production from a basal level of 78.4 ± 6.1 to 730.0 ± 53.1 pmol · mg · protein^-1 in 2 mM of sevoflurane in a dose-dependent manner. A dose of 10 µM of U73122 (a phospholipase C antagonist) significantly decreased 0.8 mM of sevoflurane-stimulated IP₃ production from 387.8 ± 24.7 to 247.8 ± 19.8 pmol · mg · protein^-1. A dose of 100 µM of (p-amylcinnamoyl) anthranilic acid (a PLA₂ antagonist) also significantly decreased sevoflurane-stimulated IP₃ production to 282.0 ± 24.0 pmol · mg · protein^-1. Exposure to 1 µM of genistein and tyrphostin A23 (tyrosine kinase inhibitors) significantly decreased sevoflurane-stimulated IP₃ production to 241.0 ± 35.3 and 267.4 ± 32.9 pmol · mg · protein^-1. Sevoflurane-stimulated IP₃ production was significantly decreased by 10 µM of 8-(N,N-diethylamino) octyl-3,4-5-trimathoxybenzoate (an intracellular calcium antagonist) and 100 µM and 1 mM of guanosine 5'-O-(2-thiodiphosphate) (GDPßS), a guanosine 5'triphosphate-binding protein inhibitor. Elevation of IP₃ production was significantly higher in halothane than in sevoflurane and isoflurane at the same concentration of 0.8 mM. We conclude that sevoflurane-stimulated IP₃ production involves phospholipase C, phospholipase A₂, tyrosine kinase, and guanosine 5'triphosphate-binding protein and the stimulation is associated with concentration of intracellular ionized calcium.

Implications: Inhaled anesthetics increase intracellular ionized calcium in the skeletal muscle cell and the ionized calcium increase is partly released from the intracellular store by inositol 1,4,5-triphosphate (IP₃) formation. IP₃ plays an important role in excitation-contraction coupling and malignant hyperthermia. We studied whether sevoflurane affects IP₃ formation and the mechanisms that modulate IP₃.

This article has been cited by other articles:

				B. Vivien, J.-S. David, J.-L. Hanouz, J. Amour, Y. Lecarpentier, P. Coriat, and B. Riou The Paradoxical Positive Inotropic Effect of Sevoflurane in Healthy and Cardiomyopathic Hamsters Anesth. Analg., July 1, 2002; 95(1): 31 - 38. [Abstract] [Full Text] [PDF]

				A. Kudoh, H. Katagai, and T. Takazawa Sevoflurane Increases Glucose Transport in Skeletal Muscle Cells Anesth. Analg., July 1, 2002; 95(1): 123 - 128. [Abstract] [Full Text] [PDF]

				B. Pouzet, J.-B. Lecharny, M. Dehoux, S. Paquin, M. Kitakaze, J. Mantz, and P. Menasche Is there a place for preconditioning during cardiac operations in humans? Ann. Thorac. Surg., March 1, 2002; 73(3): 843 - 848. [Abstract] [Full Text] [PDF]