Comparison of Peptidic and Nonpeptidic delta-Opioid Agonists on Guanosine 5'-O-(3-[~35S]thio)triphosphate([~35S]GTPgammaS)Binding in Brain Slices from Sprague-Dawley Rats

摘要

Previous studies have demonstrated that peptidic and nonpep-tidic delta-opioid receptor agonists have different effects depending on the measure.For example,nonpeptidic delta-opioid agonists,but not peptidic agonists,produce convulsions in rats,and in vitro studies suggested that peptidic and nonpeptidic delta-opioid agonists might have differential mechanisms of receptor down-regulation.The present study evaluated potential differences between peptidic and nonpeptidic delta-opioid agonists in their ability to activate G proteins using guanosine 5'-OMICRON-(3-[~35S]thio)triphos-phate([~35S]GTPgammaS)autoradiography experiments in rat brain slices.The peptidic agonist [D-Pen~2,D-Pen~5]-enkephalin and the nonpeptidic agonist(+)BW373U86 [(+)-4-[alpha(R)-alpha-[(2S,5R)-2,5-dimethyl-4-(2-propenyl)-1-piperazinyl]-(3-hydroxyphenyl)methyrj- N,N-diethylbenzamide] demonstrated concentration-dependent increases in [~35S]GTP7S binding that were attenuated by the delta-opioid antagonist naltrindole.(+)BW373U86 was more potent and efficacious than the peptidic agonist,and this difference remained consistent across brain regions where significant stimulation was observed.In addition,multiple delta-opioid compounds were evaluated for their agonist activity in this assay.These data suggested that differences between peptidic and nonpeptidic delta-opioid agonists in behavioral studies were most likely caused by differences in agonist efficacy.Finally,these data also revealed that [~35S]GTPgammaS autoradiography could be used to compare efficacy differences among agonists across various brain regions in rat brain slices.