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The GTP-binding protein, Go, regulates neuronal calcium channels

Item Type:Article
Title:The GTP-binding protein, Go, regulates neuronal calcium channels
Creators Name:Hescheler, J. and Rosenthal, W. and Trautwein, W. and Schultz, G.
Abstract:In neuronal cells, opioid peptides and opiates inhibit neurotransmitter release, which is a calcium-dependent process. They also inhibit adenylyl cyclase, presumably via the membrane signal-transducing component, Gi, a guanine nucleotide-binding protein (G-protein). 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 function. Both G-proteins are heterotrimers consisting of alpha-, beta- and gamma-subunits; the alpha-subunits can be ADP-ribosylated by an exotoxin from Bordetella pertussis (PT), which modification inhibits receptor-mediated activation of the G-protein. It was recently shown that noradrenaline, dopamine and gamma-aminobutyric acid (GABA) inhibit the voltage-dependent calcium channels in dorsal root and sympathetic ganglia; this inhibition is mimicked by intracellular application of guanine nucleotides and blocked by PT, suggesting the involvement of a G-protein. 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 cells). Pretreatment with PT almost completely abolishes the DADLE effect. The effect is restored by intracellular application of Gi and Go. As the alpha-subunit of Go (with or without beta-gamma 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.
Keywords:Calcium, Cell Line, Leucine Enkephalin, Leucine-2-Alanine Enkephalin, GTP-Binding Proteins, Glioma, Hybrid Cells, Ion Channels, Neuroblastoma, Neurons, Animals, Mice, Rats
Source:Nature
ISSN:0028-0836
Publisher:Nature Publishing Group (U.K.)
Volume:325
Number:6103
Page Range:445-447
Date:29 January 1987
Official Publication:https://doi.org/10.1038/325445a0
PubMed:View item in PubMed

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