Mu- and delta-opioid receptors inhibitorily linked to dopamine-sensitive adenylate cyclase in rat striatum display a selectivity profile toward endogenous opioid peptides different from that of presynaptic mu, delta and kappa receptors

The apparent affinities of endogenous opioid peptides for non- competitively interacting mu and delta receptors, inhibitorily linked to dopamine (DA) D-1 receptor-stimulated adenylate cyclase, were investigated in superfused rat striatal slices exposed to 40 μM DA in the presence of 10 μM of the selective D-2 receptor antagonist (-)sulpiride. In the presence of peptidase inhibitors, a comparison was made with the apparent affinities of opioid peptides toward independent presynaptic opioid receptors in brain slices. β-Endorphin_1-31 had an about 100-fold higher apparent affinity (EC₅₀: 1 nM) toward presynaptic mu-opioid receptors, mediating inhibition of the electrically evoked neocortical [³H]norepinephrine release, than for the striatal adenylate cyclase-coupled mu·receptors. In contrast, the kappa- opioid receptor agonist dynorphin A_1-13 displayed a similar apparent affinity (EC₅₀: 0.1 μM) toward these functionally different mu receptors. Both Leu- and Met-enkephalin showed only a 3-fold higher apparent affinity (EC₅₀: 30 nM) for presynaptic delta-opioid receptors, mediating inhibition of striatal [¹⁴C]acetylcholine release, than for presynaptic mu receptors. However, whereas Leu-enkephalin had a similar apparent affinity for presynaptic and adenylate cyclase-coupled delta receptors, Met-enkephalin displayed a 30-fold selectivity toward the latter receptors. Studying the inhibitory effect of Met-enkephalin on striatal adenylate cyclase stimulated by endogenously released (amphetamine-induced) DA, its very high affinity appeared to be inversely related to the activation of inhibitory DA D-2 receptors. These data reveal a unique agonist affinity profile of interacting adenylate cyclase-coupled mu and delta receptors, mediating postsynaptic inhibition of dopaminergic neurotransmission in rat striatum, with the naturally occurring opioid peptide Met-enkephalin as a highly selective agonist. The permissive role of DA D-2 receptors is discussed.