Different affinities of native alpha1B-adrenoceptors for ketanserin between intact tissue segments and membrane preparations.
The pharmacological profiles of alpha1-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 alpha1-adrenoceptors subtypes, ketanserin showed significantly lower affinity for the alpha1B-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 alpha1B-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 alpha1A- and alpha1D-adrenoceptors even though the assays were conducted under different conditions. In contrast, the affinities of alpha1A-, alpha1B-, and alpha1D-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 alpha 1B-adrenoceptors for ketanserin is strongly influenced by the assay conditions and suggest that antagonist affinity is not necessarily constant.
Sathi
Zakia Sultana
ZS
Division of Pharmacology, Department of Biochemistry and Bioinformative Sciences, University of Fukui, School of Medicine, Eiheiji-Matsuoka, Fukui 910-1193, Japan.
Anisuzzaman
Abu Syed Md
AS
Morishima
Shigeru
S
Suzuki
Fumiko
F
Tanaka
Takashi
T
Yoshiki
Hatsumi
H
Muramatsu
Ikunobu
I
D058668:Adrenergic alpha-1 Receptor Antagonists; D000317:Adrenergic alpha-Antagonists / Q000378:metabolism* / Q000494:pharmacology; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000378:metabolism*; D001158:Arteries / Q000378:metabolism; D001667:Binding, Competitive; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism*; D002540:Cerebral Cortex / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007211:Indoles / Q000378:metabolism; D007650:Ketanserin / Q000378:metabolism* / Q000494:pharmacology; D008297:Male; D010879:Piperazines / Q000378:metabolism; D011224:Prazosin / Q000378:metabolism; D011485:Protein Binding; D051381:Rats; D017208:Rats, Wistar; D018340:Receptors, Adrenergic, alpha-1 / Q000235:genetics / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism; D013347:Subcellular Fractions; D013623:Tail / Q000098:blood supply*; D014162:Transfection; D014661:Vasoconstriction
C547713:ADRA1A protein, human; C547716:ADRA1B protein, human; C547719:ADRA1D protein, human; C547715:Adra1a protein, rat; C547718:Adra1b protein, rat; C547721:Adra1d protein, rat; D058668:Adrenergic alpha-1 Receptor Antagonists; D000317:Adrenergic alpha-Antagonists; D007211:Indoles; D010879:Piperazines; D018340:Receptors, Adrenergic, alpha-1; D011994:Recombinant Proteins; D007650:Ketanserin; C095285:silodosin; C053428:BMY 7378; D011224:Prazosin