文章基本信息

标题：Binding of a Catechol Derivative of Denopamine (T-0509) and N-tert-Butylnoradrenaline (Colterol) to β1-and β2-Adrenoceptors
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作者：Toshiyuki KUSAYAMA ; Junichiro OKA ; Hideo YABANA 等
期刊名称：Biological and Pharmaceutical Bulletin
印刷版ISSN：0918-6158
电子版ISSN：1347-5215
出版年度：1994
卷号：17
期号：8
页码：1023-1028
DOI：10.1248/bpb.17.1023
出版社：The Pharmaceutical Society of Japan
摘要：The affinities for β-adrenoceptors, the subtype-selectivity and the agonistic effectiveness of T-0509 (a catechol derivative of denopamine) and colterol (N-tert-butylnoradrenaline ; Col) were compared with those of other β-agonists using a binding assay method. Specific binding of [³H] dihydroalprenolol (³H-DHA) to guinea pig left ventricular and lung membranes was saturable, and Scatchard and Hill analyses suggested that ³H-DHA bound to both membranes with a single population of binding sites with no binding site cooperativity. Addition of 5'-guanylyl-imidodiphosphate (GppNHp, 30μM) led to a rightward shift of the ³H-DHA binding displacement curves of T-0509 and Col in both membranes, and the degree of shift was similar to that of full agonists such as isoproterenol (Iso), adrenaline (Adr) and noradrenaline (NA). Both T-0509 and Col were thus considered to be full agonists at both β₁-and β₂-adrenoceptors, respectively, unlike denopamine and procaterol. T-0509 and Col showed considerably high affinity for both β₁-and β₂-adrenoceptors, and T-0509, like denopamine, was as selective for the β₁-subtype as NA (4.5-fold compared with Iso as a non-selective agonist), whereas Col was more selective for the β₂-subtype than Adr (4.5-fold compared with Iso).
关键词：β-adrenoceptor;radioligand binding;T-0509;colterol;subtype selectivity;agonistic effectiveness