| Budget Amount *help |
¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 1998: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1997: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1996: ¥600,000 (Direct Cost: ¥600,000)
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| Research Abstract |
This study was designed to determine whether the volatile anesthetics halothane and isoflurane inhibit beta-adrenoceptor-mediated responses, and which signal transduction steps are important for the inhibition if they do. We found that the volatile anesthetics used at clinically relevant concentrations can interfere with responses mediated by the beta-adrenoceptor agonist, isoproterenol. Halothane and isoflurane impaired isoproterenol-induced vasodilation and a decline of cytosolic concentrations of Ca^<2+> ([Ca^<2+>]i), whereas they only slightly affected vasodilation induced by the adenylyl cyclase activator, forskolin, and the membrane-permeable cyclic AMP, dbcAMP.This finding is consistent with the additional result that both anesthetics inhibited isoproterenol-induced, but not forskolin-induced, increases in cyclic AMP contents. Furthermore, both agents did not interfere with the ligand-binding property to the beta-adrenoceptor. These results indicate that halothane and isoflurane predominantly interfere with beta-adrenoceptor-mediated responses at the step between the beta-adrenoceptor and adenylyl cyclase ; the logical site would therefore include Gproteins.
In addition to the vasorelaxation mediated by the beta-adrenoceptor-cyclic AMP system, we also investigated the effect of halothane on the vasorelaxation mediated by the nitric oxide (NO)-cyclic GMP system. We used nitroglycerin as a NO donor. We found that halothane interfered with nitroglycerin-induced vasorelaxation in a concentration-dependent fashion. Furthermore, halothane's inhibition was govemed by both [Ca^<2+>]i-dependent and [Ca^<2+>]i-independent mechanisms.
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