Abstract
In neuronal cells, opioid peptides and opiates inhibit neuro-transmitter release, which is a calcium-dependent process1. They also inhibit adenylyl cyclase2, presumably via the membrane signal-transducing component, Gi, a guanine nucleotide-binding protein (G-protein)3,4. No causal relationship between these two events has yet been demonstrated. Besides Gi, membranes of neuronal tissues contain large amounts of Go, a G-protein with unknown function5,6. Both G-proteins are heterotrimers consisting of α-, β- and γ-subunits7; the α-subunits can be ADP-ribosylated by an exotoxin from Bordetella pertussis (PT), which modification inhibits receptor-mediated activation of the G-protein8. It was recently shown that noradrenaline, dopamine and γ-aminobutyric acid (GABA) inhibit the voltage-dependent calcium channels in dorsal root and sympathetic ganglia9–11; this inhibition is mimicked by intracellular application of guanine nucleotides and blocked by PT, suggesting the involvement of a G-protein12,13. Here we report an inhibitory effect of the opioid D-Ala2, D-Leu5-enkephalin (DADLE) on the calcium current (ICa ) in neuroblastoma x glioma hybrid cells (N x G cells14). Pretreatment with PT almost completely abolishes the DADLE effect. The effect is restored by intracellular application of Gi and Go. As the α-subunit of Go (with or without β-γ complex) is 10 times more potent than Gi, we propose that Go is involved in the functional coupling of opiate receptors to neuronal voltage-dependent calcium channels.
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Hescheler, J., Rosenthal, W., Trautwein, W. et al. The GTP-binding protein, Go9 regulates neuronal calcium channels. Nature 325, 445–447 (1987). https://doi.org/10.1038/325445a0
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DOI: https://doi.org/10.1038/325445a0
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