Mu and delta opiate receptors coupled negatively to adenylate cyclase on embryonic neurons from the mouse striatum in primary cultures.
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)
Chneiweiss
H
H
Chaire de Neuropharmacologie, INSERM U 114, Collège de France, Paris.
Glowinski
J
J
Premont
J
J
D000067956:Adenylyl Cyclase Inhibitors; D000262:Adenylyl Cyclases / Q000378:metabolism*; D000818:Animals; D002478:Cells, Cultured; D003342:Corpus Striatum / Q000166:cytology / Q000196:embryology / Q000378:metabolism*; D004622:Embryo, Mammalian / Q000378:metabolism; D004743:Enkephalin, Leucine / Q000494:pharmacology; D051379:Mice; D009474:Neurons / Q000378:metabolism*; D011957:Receptors, Opioid / Q000378:metabolism*
D000067956:Adenylyl Cyclase Inhibitors; D011957:Receptors, Opioid; D004743:Enkephalin, Leucine; D000262:Adenylyl Cyclases