Opiate receptors in neuronal primary cultures

The occurrence and characteristics of μ-, δ- and k-receptors were studied as effects of the respective agonists on forskolin-stimulated accumulation of cAMP in neuronal enriched primary cultures from the cerebral cortex of foetal rats. Morphine or [d-Ala2,N-Me-Phe4,Gly5-ol]-enkephalin (DAGO) were used as μ-receptor agonists. [d-Ala2,d-Leu5-Enkephalin (DADLE) or [d-Pen2,d-Pen5]-enkephalin (DPDPE) were used as δ -receptor agonists and dynorphin 1–13 (Dyn) or U-50, 488H were used as k-receptor agonists. In the presence of 10−8–10−5 M morphine or 10−8–10−5 M DAGO, there was a dose-related inhibition of the 10−5 M forskolin-stimulated accumulation of cAMP. The inhibitory action of morphine or DAGO was reversed by naloxone. In the presence of 10−9–10−6 M DADLE or 10−9–10−6 M DPDPE, there was also a dose-related inhibition of the forskolin-stimulated accumulation of cAMP and a similar result was obtained in the presence of 10−9–10−5 M Dyn or 10−9–10−5 M U-50,488 H. These findings indicate that neurones from the cerebral cortex in culture express μ-, δ- and k-receptors, that inhibit the forskolin-stimulated accumulation of cAMP. Administration of 10−5 M morphine and 10−6 M DADLE or 10−6 M DPDPE together, resulted in a non-additive inhibition of the forskolin-stimulated accumulation of cAMP, indicating the presence of both μ- and δ -receptors on the same population of cells.