Membrane preparations from guinea-pig brain were used to study the effects of temperature on the interaction of [3H][D-Ala2-MePhe-Gly-ol5] (DAGO), a selective μ agonist, [3H][D-Ala2, D-Leu5]enkephalin (DADLE), a nearly selective δ agonist and (±)[3H]ethylketazocine (EKC), a selective κ agonist when binding was measured in the presence of an excess of DAGO and DADLE. Binding was endothermic (ΔH0 = 10-17 kJ mol-1) and thus driven by the large increase in entropy (ΔS0 = 200-230 J mol-1K-1) for all ligands under examination. Van't Hoff plot for DAGO and DADLE showed a breakdown beyond 303 K which could have been due to lower in vitro stability of the proteins to conformational changes in the receptor proteins and/or to phase changes in the membranes. The present results do not agree with the hypothesis that agonist binding is associated with very small or negative ΔS0 (in opposition to antagonists) in view of the information transfer involved (the biological effect). © 1988.
Temperature dependence of the binding of mu, delta and kappa agonists to the opiate receptors in guinea pig brain
BOREA, Pier Andrea;GILLI, Gastone
1988
Abstract
Membrane preparations from guinea-pig brain were used to study the effects of temperature on the interaction of [3H][D-Ala2-MePhe-Gly-ol5] (DAGO), a selective μ agonist, [3H][D-Ala2, D-Leu5]enkephalin (DADLE), a nearly selective δ agonist and (±)[3H]ethylketazocine (EKC), a selective κ agonist when binding was measured in the presence of an excess of DAGO and DADLE. Binding was endothermic (ΔH0 = 10-17 kJ mol-1) and thus driven by the large increase in entropy (ΔS0 = 200-230 J mol-1K-1) for all ligands under examination. Van't Hoff plot for DAGO and DADLE showed a breakdown beyond 303 K which could have been due to lower in vitro stability of the proteins to conformational changes in the receptor proteins and/or to phase changes in the membranes. The present results do not agree with the hypothesis that agonist binding is associated with very small or negative ΔS0 (in opposition to antagonists) in view of the information transfer involved (the biological effect). © 1988.I documenti in SFERA sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
