Different affinities of native α1B-adrenoceptors for ketanserin between intact tissue segments and membrane preparations

The pharmacological profiles of α1-adrenoceptors for ketanserin, prazosin, silodosin, and BMY 7378 (8-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-8-azaspiro[4,5]decane-7,9-dione dihydrochloride) were examined under different assay conditions. Among the tested antagonists and α1-adrenoceptors subtypes, ketanserin showed significantly lower affinity for the α1B-adrenoceptor subtype in intact tissue sampled from the rat tail artery, thoracic aorta, and cerebral cortex (functional pKB and binding pKi were approximately 6), than in cerebral cortex membrane preparations or whole cell and membrane preparations of α1B-adrenoceptor transfected Human Embryonic Kidney 293T (HEK 293T) cells (pKi was approximately 8). In these tissues and cells, however, ketanserin showed a similar affinity (pKi = approximately 8) for α1A- and α1D-adrenoceptors even though the assays were conducted under different conditions. In contrast, the affinities of α1A-, α1B-, and α1D-adrenoceptors for prazosin, silodosin, and BMY 7378 did not significantly change under different assay conditions and in different tissues. The present study reveals that the pharmacological profiles of native α 1B-adrenoceptors for ketanserin is strongly influenced by the assay conditions and suggest that antagonist affinity is not necessarily constant.