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Diversity of inhibitory responses to beta2-stimulants shown by term-pregnant human myometria in vitro is partly due to differences in receptor density.

Authors :
Sakakibara T
Inoue Y
Uzue S
Tsukamoto T
Kobayashi M
Kojima M
Akahane M
Kitamura K
Kawarabayashi T
Source :
American journal of obstetrics and gynecology [Am J Obstet Gynecol] 2002 May; Vol. 186 (5), pp. 997-1004.
Publication Year :
2002

Abstract

Objective: The aims of this study were (1) to evaluate the usefulness of the new beta2-adrenergic stimulant KUR-1246 as a tocolytic agent and (2) to clarify the mechanisms that underlie the diverse inhibitory effects of beta2-stimulants that are seen in human myometria in vitro.<br />Study Design: The displacement of tritiated ([3H]) (-)CGP 12177 (0.4 nmol/L) by KUR-1246 and other beta2-stimulants was examined with human beta(1)- and beta2-receptors present on membrane fractions. The inhibitory effects of these beta2-stimulants on the term-pregnant human myometrium were compared with the use of isometric tension recording and microelectrode methods. Finally, the relationship between [3H]dihydroaloprenolol binding and the magnitude of the tocolytic effect of isoproterenol was examined.<br />Results: KUR-1246 was approximately 80 times and 7 times more selective for beta2-receptors than isoproterenol and ritodrine, respectively. The inhibitory effect of KUR-1246 was as strong as the inhibitory effect of the conventional beta2-adrenergic stimulants. A wide range of inhibitory effects was observed, even when high concentrations of isoproterenol or KUR-1246 were applied. There was a correlation between the degree to which isoproterenol suppressed contractions and the number of [3H]dihydroaloprenolol binding sites on the membrane in each muscle strip.<br />Conclusion: KUR-1246 should be a very useful beta2-adrenergic stimulant for use as a tocolytic agent because of its high selectivity for the beta2-receptor and its potent inhibitory effect. The diversity of the inhibitory effects that are induced by beta2-stimulants is at least partly due to differences in beta2-receptor density among term-pregnant human myometria.

Details

Language :
English
ISSN :
0002-9378
Volume :
186
Issue :
5
Database :
MEDLINE
Journal :
American journal of obstetrics and gynecology
Publication Type :
Academic Journal
Accession number :
12015527
Full Text :
https://doi.org/10.1067/mob.2002.122412