title: Halothane and isoflurane enhance basal and carbachol-stimulated inositol(1,4,5)triphosphate formation in SH-SY5Y human neuroblastoma cells.
abstract: The cellular mechanisms underlying the clinical effects of volatile anaesthetics remain unknown, although the plasma membrane and its associated proteins are likely targets. One such protein is the enzyme phospholipase C (PLC), which catalyses the formation of the second messenger inositol(1,4,5)triphosphate [Ins(1,4,5)P3]. Using SH-SY5Y human neuroblastoma cells we have demonstrated that halothane (0.50, 0.75 and 1.00%) enhances basal Ins(1,4,5)P3 mass formation approximately 1.8-fold. Halothane also caused a dose-dependent enhancement of carbachol-stimulated biphasic Ins(1,4,5)P3 formation at both the peak (half-maximal stimulation, EC50 = 0.76%) and plateau (EC50 = 0.74%) phases. At 1%, halothane did not alter the affinity for carbachol at either the peak (IC50: air = 9.4 +/- 1.5, halothane = 12.7 +/- 1.0 microM) or plateau (EC50: air = 11.7 +/- 1.2, halothane = 11.6 +/- 1.0 microM) phase, but did increase the maximum Ins(1,4,5)P3 response at both phases (air vs halothane: peak, 79.9 +/- 0.5 vs 124.8 +/- 2.5; plateau, 33.2 +/- 0.5 vs 47.9 +/- 0.6 pmol/mg protein). Isoflurane (2%) also enhanced basal and carbachol-stimulated Ins(1,4,5)P3 formation 2-fold and 1.5-fold, respectively. In summary, clinically relevant doses of the volatile anaesthetics halothane and isoflurane enhance basal and carbachol-stimulated Ins(1,4,5)P3 formation. Thus, activation of PLC, and subsequent potential Ins(1,4,5)P3-mediated rises in intracellular calcium, could play a part in the cellular mechanisms of volatile agent-induced anaesthesia.
authors.affiliation: University Department of Anaesthesia, Leicester Royal Infirmary, U.K.
authors.forename: D
authors.initials: D
authors.lastname: Smart
authors.forename: G
authors.initials: G
authors.lastname: Smith
authors.forename: D G
authors.initials: DG
authors.lastname: Lambert
mesh_terms: D002217:Carbachol / Q000494:pharmacology*; D006221:Halothane / Q000494:pharmacology*; D006801:Humans; D015544:Inositol 1,4,5-Trisphosphate / Q000096:biosynthesis*; D007530:Isoflurane / Q000494:pharmacology*; D009447:Neuroblastoma; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D014407:Tumor Cells, Cultured
chemical_list: D015544:Inositol 1,4,5-Trisphosphate; D002217:Carbachol; D007530:Isoflurane; D006221:Halothane