Binding thermodynamics at the human A₃ adenosine receptor

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• 作者：Merighi ; Stefania ; Varani ; Katia ; Gessi ; Stefania ; Klotz ; Karl-Norbert ; Leung ; Edward ; Baraldi ; Pier Giovanni ; et. al.
• 关键词：[³H]MRE 3008F20 ; [³H]5-N(4-methoxyphenylcarbamoyl)amino-8-propyl-2-(2-furyl)pyrazolo[4 ; 3-e]-1 ; 2 ; 4-triazolo[1 ; 5-c]-pyrimidine ; NECA ; 5&prime ; -N-ethyl-carboxamidoadenosine ; R-PIA ; R(&minus ; )N⁶(2-phenyl-isopropy
• 刊名：Biochemical Pharmacology
• 出版年：2002
• 出版时间：January 15, 2002
• 年：2002
• 卷：63
• 期：2
• 页码：157-161
• 全文大小：108 K

文摘

The thermodynamic parameters ΔG°, ΔH° and ΔS° of the binding equilibrium of six adenosine receptor agonists and five antagonists at adenosine A₃ receptors were determined by means of affinity measurements at six different temperatures (4, 10, 15, 20, 25 and 30°) and van’t Hoff plots were constructed. Affinity constants were measured on Chinese hamster ovary (CHO) cells transfected with the human A₃ receptors by inhibition assays of the binding of the selective A₃ antagonist [³H]MRE 3008F20. van’t Hoff plots were linear for agonists and antagonists in the temperature range 4–30°. Their thermodynamic parameters fall in the ranges 21≤ΔH°≤67kJmol⁻¹ and 208≤ΔS°≤410J(Kmol)⁻¹ for agonists and −52≤ΔH°≤−9kJmol⁻¹ and 16≤ΔS°≤81J(K/mol)⁻¹ for antagonists, showing that agonist binding is always totally entropy-driven while antagonist binding is enthalpy- and entropy-driven. The results are discussed with the aim of obtaining new details on the nature of the forces driving the A₃ binding at a molecular level.