Primary cultures of pure populations of neuronal or glial cells from the striatum, the cerebral cortex, and the mesencephalon of the mouse embryo were used to look for the presence of
opiate receptors coupled to
adenylate cyclase.
Leu-enkephalin inhibited cAMP production in membranes of embryonic striatal neurons but not in those of other cell types examined. Mu and delta
opiate receptors seemed to be coupled negatively to
adenylate cyclase in embryonic striatal neurons. It was found that
DTLET (a selective delta agonist), as well as
DAGO (a selective mu agonist), inhibited cAMP production on these cells.
DTLET but not, however,
DAGO produced a similar effect on homogenates from the adult rat striatum and on membranes from the
neuroblastoma x
glioma hybrid cell line NG 108-15, two preparations known to possess only
delta receptors negatively coupled to
adenylate cyclase. The selective kappa agonist U 50.488 was ineffective on all types of membrane preparations used. The inhibitory effects of both
DTLET and
DAGO on basal
adenylate cyclase activity in striatal neurons were reversed by
naloxone with a similar efficacy. Two other selective mu agonists,
trimu 5 and
morphiceptin, inhibited cAMP production in membranes of striatal neurons as well. The nonadditivity of the inhibitory effects of
DTLET and
DAGO on basal or
forskolin-induced activation of
adenylate cyclase suggested that mu and
delta receptors were colocalized on a similar subpopulation of striatal cells in primary culture. These cells possess dopaminergic receptors of the D1 subtype as well since the amplitude of the inhibitory effects of
DTLET and
DAGO on cAMP production was increased in the presence of
dopamine.(ABSTRACT TRUNCATED AT 250 WORDS)