[Kinetic characteristics of the effect of GTP on properties of opioid receptors].
Specific interactions of guanine nucleotides with rat brain membrane preparations were investigated; a two-step scheme of this interaction was proposed. The effect of GTP on the agonist binding to rat brain opioid receptors was studied. Nucleotides were shown to inhibit the ligand interactions with mu- and sigma-receptors. It was found that the GTP-induced inhibition differs from that of the GTP stable analog, GppNp, i.e., GTP does not initiate any noticeable dissociation of the receptor system component and its liberation from the membrane into solution as is the case with GppNp. A kinetic model of the GTP interactions with the opioid receptor system stipulating that the affinity of high affinity centers for mu- and delta-ligands changes after nucleotide hydrolysis on the N-protein, was proposed. The differences in the mechanisms of GTP effect on mu- and sigma-receptors were revealed, i.e., the inhibition of the ligand binding to mu-receptors may occur just after GTP binding to the N-protein. The ligand-receptor interactions in the presence of GTP were modelled according to the proposed scheme.
Skliankina
O A
OA
Kurochkin
I N
IN
Varfolomeeva
A D
AD
Krekhnov
B V
BV
Zaĭtsev
S V
SV
Varfolomeev
S D
SD
D000227:Adenine Nucleotides / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D001667:Binding, Competitive; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D004743:Enkephalin, Leucine / Q000031:analogs & derivatives*; D004745:Enkephalins / Q000378:metabolism; D006153:Guanosine Diphosphate / Q000378:metabolism / Q000494:pharmacology; D006157:Guanosine Monophosphate / Q000378:metabolism / Q000494:pharmacology; D006160:Guanosine Triphosphate / Q000378:metabolism / Q000494:pharmacology*; D007700:Kinetics; D008297:Male; D009842:Oligopeptides / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D011957:Receptors, Opioid / Q000187:drug effects / Q000378:metabolism*; D017465:Receptors, Opioid, delta; D017450:Receptors, Opioid, mu
D000227:Adenine Nucleotides; D004745:Enkephalins; D009842:Oligopeptides; D011957:Receptors, Opioid; D017465:Receptors, Opioid, delta; D017450:Receptors, Opioid, mu; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D006153:Guanosine Diphosphate; D004743:Enkephalin, Leucine; C034318:enkephalin, Ser(2), Leu(5), Thr(6)-; D006157:Guanosine Monophosphate; D006160:Guanosine Triphosphate
Kineticheskie zakonomernosti vliianiia GTP na svoĭstva opioidnykh retseptorov.