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RESEARCH PRODUCT

Supplementary Material for: Validation of Fenoterol to Study ��2-Adrenoceptor Function in the Rat Urinary Bladder

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Fenoterol is a ��2-adrenoceptor (AR)-selective agonist that is commonly used to investigate relaxation responses mediated by ��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 ��3-AR. We designed the present study to investigate whether fenoterol is a proper pharmacological tool to study ��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 (pEC50 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 ��2-AR antagonist ICI 118,551 and the ��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 (pEC50 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 (pEC50 5.03 �� 0.18). Thus, we conclude that fenoterol is a proper pharmacological tool to assess ��2-AR-mediated responses in the rat urinary bladder and most likely in other smooth-muscle preparations containing multiple subtypes of the ��-AR.