Binding thermodynamics of adenosine A2a receptor ligands

doi:10.1016/0006-2952(94)00464-W

Biochemical Pharmacology

Volume 49, Issue 4, 14 February 1995, Pages 461-469

https://doi.org/10.1016/0006-2952(94)00464-W Get rights and content

Abstract

The thermodynamic parameters ΔG °, ΔH °, and ΔS ° of the binding equilibrium of seven adenosine agonists and five xanthine antagonists binding specifically to adenosine A_2a receptors were determined by means of affinity measurements at six different temperatures (0, 10, 20, 25, 30 and 35 °) and van't Hoff plots. Affinity constants were measured on rat striatum membranes by saturation experiments for the selective A_2a agonist 2-[p-(carboxy-ethyl)-phenethylamino]-5′-(ndashethyl) carboxamidoadenosine ([³H]CGS 21680) and by inhibition assays of [³H]CGS 21680 binding for all other compounds. Scatchard plots were monophasic in the full range of temperatures, indicating a single class of high affinity binding sites whose receptor density, B_MAX, is essentially temperature independent. Van't Hoff plots were linear in the temperature range 0–30 ° for agonists and 0–35 ° for antagonists; their thermodynamic parameters fall, respectively, in the ranges 7 ⩽ ΔH ° ⩽ 50 kJ/mol and 177 ⩽ ΔS ° ⩽ 278 J K⁻¹ mol⁻¹ and −36 ⩽ ΔH ° ⩽ −7 kJ/mol and $−33 ⩽ ΔS ° ⩽ 94 J K^{−1} mol^{−1}$ , showing that agonist binding is entropy-driven while antagonist binding is enthalpy-driven. The results are compared with those already reported for the binding of the same compounds to rat brain minus striatum adenosine A₁ receptors obtained by displacing [³H]CHA as A₁ selective radioligand (Borea PA et al., Mol Neuropharmacol2: 273–281, 1992). The comparison suggests that the two receptors are very similar as far as their binding sites are concerned and possibly philogenetically related. The analysis of thermodynamical data makes it possible to propose an analogical model of drug-receptor interaction which may account for both affinity and intrinsic activity properties.

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Research paperBinding thermodynamics of adenosine A2a receptor ligands

Abstract

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J Pharmacol Exp Ther

Thermodynamic properties of agonist interactions with the β-adrenergic receptor-coupled adenylate cyclase system. II. Agonist binding to soluble β-adrenergic receptors

J Pharmacol Exp Ther

The binding of agonists and antagonists to rat lung β-adrenergic receptors as investigated by thermodynamics and structure-activity relationships

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Research paper
Binding thermodynamics of adenosine A_2a receptor ligands