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| Item Type: | Article |
|---|---|
| Title: | The GTP-binding protein, Go, regulates neuronal calcium channels |
| Creators Name: | Hescheler, J., Rosenthal, W., 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 |
| 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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