Dog cerebral cortex contains μ-, δ- and κ-opioid receptors at different densities: apparent lack of evidence for subtypes of the κ-receptor using selective radioligands

摘要: Abstract The biochemical and pharmacological properties of mu (μ), kappa (κ) delta (δ) opioid receptors were ascertained in dog cerebral cortex homogenates. selective peptides, [3H] d -Pen2- -Pen5enkephalin ([3H]DPDPE) -Ala2-MePhe4-Glyol5-enkephalin ([3H]Glyol; [3H]DAMGO), bound to δ- μ-opioid with high affinity (dissociation constants, Kdvalues= 4.7and1.6nM) but different densities binding sites (Bmax values 49.2 6.6 fmol/mg protein, respectively) washed homogenates cortex. In contrast, the non-peptides, [3H]U69593 ([3H]U69) [3H]etorphine ([3H]ET), labeled a concentration κ-opioid (respectiveBmax 67.2 76.6 protein) (respectiveKds 1.4 0.47 nM) same tissue Thus, relative rank order receptor was:κ > δ ≫ μ. labeling κ-receptors two drugs ([3H]U69 [3H]ET) failed reveal possible existence multiple κ-sites based on relativeBmax radioglands. This conclusion was further supported by similarity specificity both [3H]U69 [3H]ET binding, where all opioids tested produced 100% inhibition these labels potency at inhibiting probes was:U50488 >U69593 >dynophin-(1–8) >naloxone≫morphine≫Glyol (DAMGO)>DPDPE. fact that [3H]Glyol selectively μ-receptors borne-out inhibitory compounds against membranes, thus:Glyol (DAMGO)>morphine>naloxone>dynorphin-(1–8) ≫U50488 >U69593. selectivity [3H]DPDPE δ-receptors other subtypes, being:DPDPE>dynorphin-(1–8) >naloxone>morphine⩾glyol≫U69 >U50488. These data have therefore helped identify presence μ-, cortex, shown lack subtypes κ-receptor this tissue.