Endomorphins inhibit high‐threshold Ca2+ channel currents in rodent NG108‐15 cells overexpressing μ‐opioid receptors

Abstract
1 Extracellular application of the novel brain peptides endomorphin 1 (EM1) and endomorphin 2 (EM2) inhibited high-threshold Ca2+ channel currents in NGMO-251 cells, a daughter clone of NG108-15 mouse neuroblastoma × rat glioma hybrid cells, in which μ-opioid receptors are overexpressed. 2 In contrast, EM1 and EM2 did not induce this inhibition in the parental NG108-15 cells that predominantly express endogenous δ-receptors. 3 The IC50 for EM1 and EM2 was 7.7 and 23.1 nm, respectively. 4 EM-induced Ca2+ channel current inhibition was blocked by treatment or pretreatment of the cells with 100 μmN-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 with cloned μ-receptors, which couple via Gi/Go-type G proteins, and that EMs fulfill one of the necessary synaptic conditions for them to be identified as neurotransmitters.