Abstract

The apparent affinities of endogenous opioid peptides for noncompetitively 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 microM DA in the presence of 10 microM 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. beta-Endorphin 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 A1-13 displayed a similar apparent affinity (EC50: 0.1 microM) 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.(ABSTRACT TRUNCATED AT 250 WORDS)