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

Nature. 1987 Jan 29-Feb 4;325(6103):445-7. doi: 10.1038/325445a0.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Calcium / metabolism*
  • Cell Line
  • Enkephalin, Leucine / analogs & derivatives
  • Enkephalin, Leucine / pharmacology
  • Enkephalin, Leucine-2-Alanine
  • GTP-Binding Proteins / physiology*
  • Glioma
  • Hybrid Cells / physiology
  • Ion Channels / drug effects
  • Ion Channels / physiology*
  • Mice
  • Neuroblastoma
  • Neurons / physiology*
  • Rats

Substances

  • Ion Channels
  • Enkephalin, Leucine
  • Enkephalin, Leucine-2-Alanine
  • GTP-Binding Proteins
  • Calcium