Opiate receptors in neuronal primary cultures.

The occurrence and characteristics of mu-, delta- and kappa-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 mu-receptor agonists. [D-Ala2,D-Leu5]-Enkephalin (DADLE) or [D-Pen2,D-Pen5]-enkephalin (DPDPE) were used as delta-receptor agonists and dynorphin 1-13 (Dyn) or U-50,488H were used as kappa-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 mu-, delta- and kappa-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 mu- and delta-receptors on the same population of cells.