Diversity of inhibitory responses to β2-stimulants shown by term-pregnant human myometria in vitro is partly due to differences in receptor density

Objective: The aims of this study were (1) to evaluate the usefulness of the new β2-adrenergic stimulant KUR-1246 as a tocolytic agent and (2) to clarify the mechanisms that underlie the diverse inhibitory effects of β2-stimulants that are seen in human myometria in vitro. Study Design: The displacement of tritiated ([3H]) (−)CGP 12177 (0.4 nmol/L) by KUR-1246 and other β2-stimulants was examined with human β1- and β2-receptors present on membrane fractions. The inhibitory effects of these β2-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. Results: KUR-1246 was approximately 80 times and 7 times more selective for β2-receptors than isoproterenol and ritodrine, respectively. The inhibitory effect of KUR-1246 was as strong as the inhibitory effect of the conventional β2-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. Conclusion: KUR-1246 should be a very useful β2-adrenergic stimulant for use as a tocolytic agent because of its high selectivity for the β2-receptor and its potent inhibitory effect. The diversity of the inhibitory effects that are induced by β2-stimulants is at least partly due to differences in β2-receptor density among term-pregnant human myometria. (Am J Obstet Gynecol 2002;186:997-1004.)