Functional, biochemical and molecular biological evidence for a possible β 3 ‐adrenoceptor in human near‐term myometrium

The possible existence of a β 3 ‐adrenoceptor (β 3 ‐AR) in human near‐term myometrium was investigated by in vitro functional and biochemical studies and analysis of mRNA expression. SR 59119A and SR 59104A and CGP 12177 (two selective agonists and a partial agonist, respectively, of the β 3 ‐AR), salbutamol and terbutaline (β 2 ‐AR agonists) each produced a concentration‐dependent relaxation of the myometrial spontaneous contractions. There were no differences in pD 2 values for the relaxing potencies of terbutaline, salbutamol, CGP 12177 and SR 59119A. The rank order for their relaxing efficacies was SR 59119A>SR 59104A>terbutaline∼salbutamol∼CGP 12177 (E max =52±7%, 42±12% and ∼ 30% respectively). Propranolol, a β 1 ‐ and β 2 ‐AR antagonist, and ICI 118551, a β 2 ‐AR antagonist (both at 0.1 μ M ), did not affect the SR 59119A‐induced relaxation whereas SR 59230A, a selective β 3 ‐AR antagonist (1 μ M ), significantly reduced the maximal relaxing effect of SR 59119A. SR 59119A and salbutamol induced a significant increase in cyclic AMP levels that was antagonized by SR 59230A but not by propranolol for SR 59119A, and by propranolol but not by SR 59230A for salbutamol. The β 3 ‐AR mRNA was positively expressed in myometrium preparations in a reverse transcription polymerase chain assay. The results presented provide the first evidence for the existence of the β 3 ‐AR subtype in human near‐term myometrium and suggest that the effects of SR 59119A might be mediated through an increase in cyclic AMP level.British Journal of Pharmacology (2000) 130 , 1960–1966; doi: 10.1038/sj.bjp.0703491