Life Sciences 67 (2000) 503—508 0024-3205/00/$ — see front matter ' 2000 Elsevier Science Inc. All rights reserved. PII: S0024-3205(00)00652-4 Comparison of [ 3 H]tamsulosin and [ 3 H]prazosin binding to wild-type and constitutively active  1B -adrenoceptors Peter Hein a , Mark Goepel a , Susanna Cotecchia b , Martin C. Michel a, * a Depts. of Medicine and Urology, University of Essen, Nephrol. Lab. IG 1, Klinikum Essen, Hufelandstr. 55, 45122 Essen, Germany b Dept. of Pharmacology, Universit de Lausanne, Lausanne, Switzerland Abstract We have tested the hypothesis that smaller  1B -adrenoceptor labeling by [ 3 H]tamsulosin compared to [ 3 H]prazosin is related to differential recognition of agonist low afnity states. Paired saturation binding experiments with [ 3 H]prazosin and [ 3 H]tamsulosin were performed in membrane preparations from rat liver and Rat-1 broblasts stably transfected with wild-type hamster  1B -adrenoceptors or a constitutively active mutant thereof. In all three settings [ 3 H]tamsulosin labeled signicantly fewer  1B -adrenoceptors than [ 3 H]prazosin. In noradrenaline competition binding experiments, the percent- age of agonist low afnity sites was smallest for the constitutively active  1B -adrenoceptor but the per- centage of agonist low afnity sites recognized by [ 3 H]tamsulosin and [ 3 H]prazosin did not differ sig- nicantly. We conclude that [ 3 H]tamsulosin labels fewer  1B -adrenoceptors than [ 3 H]prazosin but this is not fully explained by a poorer labeling of agonist low afnity sites. ' 2000 Elsevier Science Inc. All rights reserved. Keywords: [ 3 H]Prazosin; [ 3 H]Tamsulosin;  1B -Adrenoceptor; Constitutively active receptor; Radioligand binding Introduction Radioligand binding studies are an important tool in the molecular characterization of re- ceptors and for investigations on physiological, pathophysiological and drug-induced regula- tion of receptor number. The use of results from radioligand binding experiments usually relies on the assumption that the radioligand specically binds to the receptor of interest with a 1:1 stochiometry, and hence the calculated B max for the radioligand is assumed to represent the number of receptors in the tissue of interest. Recently the validity of this assumption has been questioned by showing that [ 3 H]tamsulosin labels a different number of  1 -adrenoceptors than [ 3 H]prazosin in rat hippocampus and spleen * Corresponding author. Tel.: +49-201-723-4467; fax: +49-201-723-5963. E-mail address: martin.michel@uni-essen.de (M.C. Michel)