このエントリーをはてなブックマークに追加
ID 34946
file
creator
Kurokawa, Hiromi
Matsunaga, Aki
Yuge, Osafumi
subject
Propofol
β-adrenoreceptor
Phosphodiesterase-III inhibitor
Olprinone
NDC
Medical sciences
abstract
Propofol has been shown to attenuate β-adrenoreceptor-mediated signal transduction in cardiomyocytes. Cyclic adenosine monophosphate (cAMP) is an essential second messenger of β-signal transduction, while olprinone, a phosphodiesterase-III inhibitor, improves poor cardiac performance by increasing cAMP levels. In the present study, we investigated the effects of olprinone toward the reducing effect of propofol on β-adrenoreceptor-mediated increases in cAMP production. First, suspensions of rat ventricular myocytes were incubated with isoproterenol or olprinone and the effects on cAMP concentrations were assessed. Next, propofol was added prior to the addition of isoproterenol or olprinone. Finally, following preincubation with propofol, isoproterenol with or without olprinone was added. Both isoproterenol and olprinone increased cAMP production in a dose-dependent manner. However, clinically relevant concentrations of olprinone (up to 10-7 M) did not cause a significant increase. Propofol (l0-7-10-4 M) attenuated isoproterenol-stimulated increases in cAMP production (decrease of 2 ± 4% - 43 ± 1%, as compared to the isoproterenol-stimulated state). However, the agent did not alter olprinone (10- 7 M)-stimulated cAMP production. Olprinone (10- 8 -10-6 M) reversed the attenuating effect of propofol (l0-5 M) toward isoproterenol (l0-7 M)-stimulated cAMP production dose-dependently (increase of 10 ± 5% - 79 ± 4% as compared to the propofolattenuated state). Our results suggest that an improvement in cardiac function is provided by olprinone when the β-adrenoreceptor-mediated signaling pathway is inhibited by propofol.
journal title
Hiroshima Journal of Medical Sciences
volume
Volume 57
issue
Issue 1
start page
1
end page
6
date of issued
2008-03
publisher
Hiroshima University Medical Press
issn
0018-2052
ncid
language
eng
nii type
Departmental Bulletin Paper
HU type
Departmental Bulletin Papers
DCMI type
text
format
application/pdf
text version
publisher
rights
(c) Hiroshima University Medical Press.
department
University Medical Hospital
Graduate School of Biomedical Science
他の一覧