ENDOMORPHINS INHIBIT HIGH-THRESHOLD CA2-15 CELLS OVEREXPRESSING MU-OPIOID RECEPTORS( CHANNEL CURRENTS IN RODENT NG108)

Extracellular application of the novel brain peptides endomorphin 1 (E M1) and endomorphin 2 (EM2) inhibited high-threshold Ca2+ channel curr ents in NGM0-251 cells, a daughter clone of NG108-15 mouse neuroblasto ma x rat glioma hybrid cells, in which mu-opioid receptors are overexp ressed. 2. In contrast, EM1 and EM2 did not induce this inhibition in the parental NG108-15 cells that predominantly express endogenous delt a-receptors. 3. The IC50 for EM1 and EM2 was 7.7 and 23.1 nM, respecti vely. 4. EM-induced Ca2+ channel current inhibition was blocked by tre atment or pretreatment of the cells with 100 mu M N-methylmaleimide or 100 ng ml(-1) pertussis toxin. 5. These results show that a decrease in conductance of Ca2+ channels results following interaction of EMs w ith cloned mu-receptors, which couple via G(i)/G(o)-type G proteins, a nd that EMs fulfill one of the necessary synaptic conditions for them to be identified as neurotransmitters.