Differences in the effects of β2- and β3-adrenoceptor agonists on spontaneous contractions of human nonpregnant myometrium

Objective: This study aimed to compare the relaxant properties of BRL 37344 with beta(2)-adrenoceptors agonist ritodrine on the contractility of human nonpregnant myometrium. Material and methods: The activity of myometrial strips mounted in an organ bath was recorded under isometric conditions using force transducers with digital output. Contractility before and after cumulative additions of both uterorelaxants and with preincubation with beta-adrenoceptor antagonists bupranolol, propranolol, and butoxamine were studied. Results: Both BRL 37344 (10(-10) - 10(-4) mol/L) and ritodrine (10(-10) - 10(-5) mol/L) decreased the area under curve, or AUC, value (logIC(50) -6.45 +/- 0.18 and -8.71 +/- 0.35, respectively), and the degree of inhibition of spontaneous contractile activity was similar (< 30%). However, BRL 37344 decreased the mean frequency of contractions, whereas ritodrine decreased the mean amplitude of contractions. The inhibition of contractions by BRL 37344 was partially antagonized by bupranolol and propranolol, but not with butoxamine. The inhibition by ritodrine was counteracted by all these antagonists. Conclusions: The effects of BRL37344 and ritodrine on human nonpregnant myometrium are quantitatively similar in respect to the inhibition of spontaneous contractility yet are also distinct due to their substantially different influences on contraction parameters. Our data indicate that beta(3)-adrenoceptor activation is not the sole effect of BRL 37344 on this tissue.