Characterization of Alpha-and Beta-Adrenergic and Angiotensin Receptors in Cultured Vascular Smooth Muscle Cells of Rat aorta : THE 14th CONFERENCE ON THE PATHOGENESIS OF HYPERTENSION
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概要
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To study the cellular mechanism of vascular responsiveness by vasoactive hormones, such as catecholamines and angiotensin (A), the vascular smooth muscle cells (VSMC) of two clonal cell line (A7r5 and A 10) from rat embryo, and of adult rat aorta were established in culture. Binding studies using ^<125>I-labeled-hydroxyphenylethylaminoethyltetralone as an α-adrenergic ligand and ^<125>I-labeled-iodocyanopindolol as a β-adrenergic ligand, revealed that cultured VSMCs contain both α- and β-adrenergic receptors ; the binding was specific, rapid, reversible, and saturable. α-Adrenergic receptors appear to be a single class of high-affinity binding sites with an apparent dissociation constant (K_d) of 〜 2× 10^<-10> M and a maximal binding capacity (B_<max>) of 〜300,000-400,000 sites/cell, and exclusively of α_1-subtype that is responsible for smooth muscle contraction. On the other hand, β-adrenergic receptors show almost comparable characteristics with the apparent K_d of 〜 -0.7-1.1 10^<-10> M and B_<max> of 50,000-130,000 sites/cell, and consist predominantly of _2-subtype that mediates smooth muscle relaxation. Furthermore, -adrenergic receptors are coupled to adenylate cyclase system, of which activation by -agonists induces intracellular cyclic AMP formation. In contrast, the binding of ^<125>I-labeled-AII was demonstrated only in A7r5. The binding declined rapidly during incubation possibly due to faster degradation of AII by proteolytic enzyme (s). AII receptors appear to be a single class of high-affinity binding sites with the apparent K_d of 0.9 10^<-10> M and B_<max> of 11,000 sites/cell, of which affinity is higher than any of vascular AII receptors previously reported. Therefore, cultured VSMCs isolated from neurogenic and systemic influence should provide a valuable in vitro system to investigate the characteristics of specific receptors for vasoactive hormones, the cellular mechanisms involved in activation and regulation of the receptors and subsequent biochemical responses.
- 社団法人日本循環器学会の論文
- 1985-09-20
著者
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HIRATA YUKIO
Hypertension-Endocrine Division, National Cardiovascular Center Research Institute
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Hirata Yukio
Hypertension Division National Cardio-vascurar Center Reseach Institute
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Ikeda M
Hypertension-endocrine Division National Cardiovascular Center Research Institute
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TOMITA MASAHIRO
Hypertension-Endocrine Division, National Cardiovascular Center Research Institute
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IKEDA MASAO
Hypertension-Endocrine Division, National Cardiovascular Center Research Institute
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Hirata Yukio
Tokyo Metropolitan Inst. Neurosciences Tokyo Jpn
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Tomita Masahiro
Hypertension-endocrine Division National Cardiovascular Center Research Institute
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