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Zaĭtsev, SV, Sergeeva, MG, Chichenkov, ON, Petrov, VE and Varfolomeev, SD (1986) [Changes in the properties of brain opiate receptors during the development of morphine tolerance in rats]. Biokhimiia 51:1334-40
The effects of prolonged administration of morphine on the properties of opiate receptors of rat brain were studied. For this purpose the isotherms of binding of labeled mu-, delta-, and chi-ligands--morphine, D-Ala2, D-Leu5-enkephalin and ethylketocyclazocine--with brain membrane preparations of morphine-tolerant rats as well as those of control animals were analyzed. For quantitative determination of dissociation constants of the ligand-receptor complexes (K) and receptor concentrations ([Q]), the difference and simulation methods were used. It was shown that the values of K and [Q] vary within broad ranges in individual animals, whereas the individual variations of the [Q]/[K] ratios in controls or in morphine-tolerant rats are not so significant. This suggests [Q]/K to be one of the basic criteria for a comparison of properties of opiate receptors in different groups of animals. The use of this criterion and of the simulation method demonstrated that the development of tolerance causes changes in the properties of delta-receptors (the [Q]/K ratio decreases by greater than 50%). Unlike delta-receptors, the tolerance has no appreciable effect on the properties of mu- or chi-receptors or on the superhigh affinity binding sites of the ligands tested.
Animals; Brain/metabolism; Enkephalin, Leucine/analogs & derivatives; Enkephalin, Leucine/metabolism; Enkephalin, Leucine-2-Alanine; Kinetics; Male; Morphine/metabolism; Morphine Dependence/metabolism; Morphine Dependence/physiopathology; Radioligand Assay; Rats; Rats, Inbred Strains; Receptors, Opioid/metabolism; Receptors, Opioid/physiology
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