2004 Fiscal Year Final Research Report Summary
The interaction of intravenous anesthetic agent with adrenoceptor stimulation in rat myocytes
| Project/Area Number |
14571444
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Anesthesiology/Resuscitation studies
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| Research Institution | Hiroshima University |
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Principal Investigator |
KUROKAWA Hiromi Hiroshima University, Graduate School of Biomedical Sciences, Assistant, 大学院・医歯薬学総合研究科, 助手 (20335673)
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| Co-Investigator(Kenkyū-buntansha) |
TANAKA Hiroyuki Hiroshima University, Graduate School of Biomedical Sciences, Assistant, 大学院・医歯薬学総合研究科, 助手 (10274086)
YUGE Osafumi Hiroshima University, Graduate School of Biomedical Sciences, Professor, 大学院・医歯薬学総合研究科, 教授 (40034128)
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| Project Period (FY) |
2002 – 2004
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| Keywords | intravenous anesthetic agent / myocyte / β-signaling pathway / catecholamine |
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| Research Abstract |
Background : We previously reported that propofol attenuated β-adrenoreceptor-mediated signal transduction in cardiomyocytes (ASA2000, Anesthesiology 2002). Those results suggested that it is important to use propofol carefully for critically ill patients receiving catecholamines for hemodynamic support. Cyclic adenosine monophosphate (cAMP) is an important second messenger of intracellular β-adrenoreceptor-mediated signal transduction. Thus we used cAMP to investigate the effects of β-stimulant and propofol.
First experiment : Olprinone, a phosphodiesterase-III inhibitor, improves poor cardiac performance by increasing cAMP level without an increase in O2 consumption. Thus, we hypothesized that olprinone could reverse the reducing effect of propofol on the isoproterenol-stimulated increase in cAMP production. Result : Olprinone reversed the attenuated production of cAMP caused by propofol on isoproterenol-stimulated cAMP production. Our results suggest that improvement of cardiac function is potentially provided by olprinone, when the β-adrenoreceptor-mediated signaling pathway is inhibited by propofol. (Anesthesiology 2004;101:A637)
Second experiment : Cholera toxin (CTX) exerts an influence on G-protein by ADP-ribosylation of the stimulatory G protein alpha isoform. Thus, we investigated the effective site of action for propofol in greater detail as well as its effect on CTX-stimulated cyclic adenosine monophosphate (cAMP). Result : CTX increases cAMP by ADP-ribosylation of the stimulatory G protein alpha isoform and propofol was shown to potentiate this CTX-stimulated increase in cAMP production. Our results suggest that G protein contributes to the effective site of action for propofol. (Anesthesia & Analgesia 2005;100:S37)
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