Functional, biochemical and molecular biological evidence for a possible beta(3)-adrenoceptor in human near-term myometrium

1 The possible existence of a beta(3)-adrenocepror (beta(3)-AR) in human ne ar-term myometrium was investigated by in vitro functional and biochemical studies and analysis of mRNA expression. 2 SR 59119A and SR 59104A and CGP 12177 (two selective agonists and a parti al agonist, respectively, of the beta(3)-AR), salbutamol and terbutaline (b eta(2)-AR agonists) each produced a concentration-dependent relaxation of t he myometrial spontaneous contractions. There were no differences in pot va lues for the relaxing potencies of terbutaline, salbutamol, CGP 12177 and S R 59119A. The rank order for their relaxing efficacies was SR 59119A > SR 5 9104A > terbutaline approximate to salbutamol approximate to CGP 12177 (E-m ax = 52 +/- 7%, 42 +/- 12% and approximate to 30% respectively). 3 Propranolol, a beta(1)- and beta(2)-AR antagonist, and ICI 118551, a beta (2)-AR antagonist (both at 0.1 mu M), did not affect the SR 59119A-induced relaxation whereas SR 59230A, a selective beta(3)-AR antagonist (1 mu M), s ignificantly reduced the maximal relaxing effect of SR 59119A. 4 SR 59119A and salbutamol induced a significant increase in cyclic AMP lev els that was antagonized by SR 59230A but not by propranolol for SR 59119A, and by propranolol but not by SR 59230A for salbutamol. 5 The beta(3)-AR mRNA was positively expressed in myometrium preparations i n a reverse transcription polymerase chain assay. 6 The results presented provide the first evidence for the existence of the beta(3)-AR subtype in human near-term myometrium and suggest that the effe cts of SR 59119A might be mediated through an increase in cyclic AMP level.