Temperature dependence of the binding of mu, delta and kappa agonists to the opiate receptors in guinea-pig brain.
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 mu agonist, [3H][D-Ala2,D-Leu5]enkephalin (DADLE), a nearly selective delta agonist and (+/-)[3H]ethylketazocine (EKC), a selective kappa agonist when binding was measured in the presence of an excess of DAGO and DADLE. Binding was endothermic (delta H0 = 10-17 kJ mol-1) and thus driven by the large increase in entropy (delta S0 = 200-230 J mol-1 K-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 delta S0 (in opposition to antagonists) in view of the information transfer involved (the biological effect).
Borea
P A
PA
Istituto di Farmacologia, Università di Ferrara, Italy.
Bertelli
G M
GM
Gilli
G
G
D000818:Animals; D001921:Brain / Q000378:metabolism*; D003496:Cyclazocine / Q000031:analogs & derivatives* / Q000378:metabolism; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D004743:Enkephalin, Leucine / Q000031:analogs & derivatives* / Q000378:metabolism; D016308:Enkephalin, Leucine-2-Alanine; D004745:Enkephalins / Q000378:metabolism*; D016314:Ethylketocyclazocine; D006168:Guinea Pigs; D011957:Receptors, Opioid / Q000187:drug effects / Q000378:metabolism*; D017465:Receptors, Opioid, delta; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu; D013696:Temperature
D004745:Enkephalins; D011957:Receptors, Opioid; D017465:Receptors, Opioid, delta; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D016314:Ethylketocyclazocine; D004743:Enkephalin, Leucine; D016308:Enkephalin, Leucine-2-Alanine; D003496:Cyclazocine