RT Journal Article
SR Electronic
T1 Thermodynamic analysis of agonist and antagonist binding to membrane-bound and solubilized A1 adenosine receptors.
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 1463
OP 1474
VO 266
IS 3
A1 V Casadó
A1 G Allende
A1 J Mallol
A1 R Franco
A1 C Lluis
A1 E I Canela
YR 1993
UL http://jpet.aspetjournals.org/content/266/3/1463.abstract
AB The thermodynamic properties of the agonist [Adenine-2,8-3H, ethyl-2(3)-H]-N6-phenylisopropyladenosine ([3H]R-PIA) and the antagonist 8-Cyclopentyl-1,3-[3H]dipropylxanthine ([3H]DPCPX) binding to membrane-bound and 3-3[-(choloamidopropyl)-dimethylammoniol-1-propanesulfonate/ digitonin- solubilized A1 adenosine receptors from pig brain cortex were evaluated. Rate constants for [3H]R-PIA and [3H]DPCPX association (k+1) and dissociation (k-1) processes to this receptor subtype were measured from association-dissociation experiments at six different temperatures. The values for equilibrium association constant (KA = 1/KD) were derived from rate constant values (k+1/k-1). The antagonist binding to membrane-bound receptors, the agonist binding to fast kinetic component membrane-bound receptors and the agonist binding to soluble receptors showed a linear temperature-dependence of the standard free-energy change. The first two processes are enthalpy- and entropy-driven, and the third process is enthalpy-driven with entropy working against it. On the other hand, a curvilinear temperature-dependence appears in the agonist binding to slow kinetic component membrane-bound receptors and in the antagonist binding to soluble receptors, but analyzing the semireactions (association-dissociation) involved in each case reveals that the thermodynamic behavior is very different. The thermodynamic similarities and differences are discussed in terms of receptor--G protein interaction.