Opiate receptor binding affected by guanine nucleotide. Partial loss of sensitivity to guanosine-5'-(beta,gamma-imido)triphosphate evident in vitro.
The sensitivity of the receptor dissociation rate of the opiate agonist [3H]etorphine to the effects of guanosine-5'-(beta, gamma-imido)triphosphate and Na+ was measured in washed rat brain membrane homogenates after in vivo labeling. Comparison to the previously measured rapid in vivo dissociation curve (t1/2 approximately 50 s) (Perry, D. C., Rosenbaum, J. S., Kurowski, M., and Sadée, W. (1982) Mol. Pharmacol. 21, 272-279) revealed that brain homogenization and membrane washing procedures significantly prolonged the dissociation rate, even when measured in the presence of Na+ and guanyl nucleotide. The in vivo dissociation rate could only be reproduced in vitro when labeling occurred in vivo and brain homogenization occurred in the presence of these regulatory factors. The prolonged in vitro [3H]etorphine dissociation curve was predominately a result of a decreased sensitivity to guanine nucleotide rather than to Na+. These data suggest that partial functional uncoupling of the opiate receptor-effector system may occur in vitro.
D000818:Animals; D001921:Brain / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism; D005048:Etorphine / Q000378:metabolism; D006160:Guanosine Triphosphate / Q000031:analogs & derivatives*; D006165:Guanylyl Imidodiphosphate / Q000494:pharmacology*; D007700:Kinetics; D051381:Rats; D011957:Receptors, Opioid / Q000187:drug effects / Q000378:metabolism*
D011957:Receptors, Opioid; D006165:Guanylyl Imidodiphosphate; D005048:Etorphine; D006160:Guanosine Triphosphate