Validation of Fenoterol to Study beta(2)-Adrenoceptor Function in the Rat Urinary Bladder

Fenoterol is a beta(2)-adrenoceptor (AR)-selective agonist that is commonly used to investigate relaxation responses mediated by beta(2)-AR in smooth muscle preparations. Some data have questioned this because fenoterol had low potency in the rat urinary bladder when a muscarinic agonist was used as a pre-contraction agent and because some investigators proposed that fenoterol may act in part via beta(3)-AR. We designed the present study to investigate whether fenoterol is a proper pharmacological tool to study beta(2)-AR-mediated relaxation responses in the rat urinary bladder. Firstly, we have compared the effect of pre-contraction agents on fenoterol potency and found that fenoterol potency was about 1.5 log units greater against KCl than carbachol (pEC(50) 7.19 +/- 0.66 and 5.62 +/- 1.09 of KCl and of carbachol, respectively). To test the selectivity of fenoterol, we have determined the effects of the beta(2)-AR antagonist ICI 118,551 and the beta(3)-AR antagonist L 748,337 on relaxation responses to fenoterol. While 300 nM L 748,337 had little effect on the potency of fenoterol (pEC(50) 6.56 +/- 0.25 and 6.33 +/- 0.61 in the absence and presence of L 748,337, respectively), the relaxation curve for fenoterol was right-shifted in the presence 300 nM ICI 118,551 (pEC(50) 5.03 +/- 0.18). Thus, we conclude that fenoterol is a proper pharmacological tool to assess beta(2)-AR-mediated responses in the rat urinary bladder and most likely in other smooth-muscle preparations containing multiple subtypes of the beta-AR. (c) 2021 S. Karger AG, Basel