The binding of agonists and antagonists to rat lung beta-adrenergic receptors as investigated by thermodynamics and structure-activity relationships.
The binding of agonists and antagonists to rat lung beta-adrenergic receptors as investigated by thermodynamics and structure-activity relationships.
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通过热力学和结构活性关系研究激动剂和拮抗剂与大鼠肺β-肾上腺素能受体的结合。
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发表时间：
1986
期刊：
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通讯作者：
J. Tillement
中科院分区：
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作者：
F. Brée;N. El Tayar;H. van de Waterbeemd;B. Testa;J. Tillement
以大鼠肺膜为β-肾上腺素能受体来源，研究了几种激动剂和拮抗剂与相关β受体的体外相互作用。检查了温度（4 ℃至37 ℃）对β-肾上腺素能激动剂和拮抗剂从β-肾上腺素能受体置换（-）-[125 I]碘氰基吲哚洛尔的能力的影响。从由此获得的Kj值计算热力学参数。还使用RP-HPLC方法测量二十个分子的亲脂性。所得结果表明：受体密度不受温度的影响，但它们与20种受体激动剂和拮抗剂的亲和力随温度的降低而增加，受体激动剂的结合是焓驱动的，而受体拮抗剂的结合是熵驱动的，亲脂性受体激动剂多巴酚丁胺除外;所有20种化合物都存在熵和亲脂性之间的单一关系，这表明分子结构和物理化学性质结合的热力学。
Interaction of several agonists and antagonists with the relevant beta receptor were studied in vitro using rat lung membranes as beta-adrenergic receptor source. The influence of temperature, between 4 degrees C and 37 degrees C, on the ability of beta-adrenergic agonists and antagonists to displace (-)-[125I]iodocyanopindolol from beta-adrenergic receptors was checked. Thermodynamic parameters were calculated from the Kj values thus obtained. Lipophilicity of the twenty molecules was also measured using a RP-HPLC method. The results obtained show: the density of receptors was not affected by the temperature but their affinity for the twenty agonists and antagonists increased with decreasing temperature; the binding of agonists is enthalpy driven while that of antagonists is entropy driven, with the exception of the lipophilic agonist dobutamine; a single relationship between entropy and lipophilicity exists for all twenty compounds and would suggest that molecular structure and physicochemical properties account for the thermodynamics of binding.