G-protein-independent signaling by G-protein-coupled receptors

Trends Neurosci. 2000 Oct;23(10):469-75. doi: 10.1016/s0166-2236(00)01643-x.


Two classes of receptors transduce neurotransmitter signals: ionotropic receptors and heptahelical metabotropic receptors. Whereas the ionotropic receptors are structurally associated with a membrane channel, a mediating mechanism is necessary to functionally link metabotropic receptors with their respective effectors. According to the accepted paradigm, the first step in the metabotropic transduction process requires the activation of heterotrimeric G-proteins. An increasing number of observations, however, point to a novel mechanism through which neurotransmitters can initiate biochemical signals and modulate neuronal excitability. According to this mechanism metabotropic receptors induce responses by activating transduction systems that do not involve G-proteins.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Gene Expression Regulation
  • Heterotrimeric GTP-Binding Proteins / physiology*
  • Humans
  • Invertebrates / physiology
  • MAP Kinase Signaling System / drug effects
  • Models, Neurological*
  • Nerve Tissue Proteins / physiology*
  • Neurotransmitter Agents / pharmacology
  • Receptor Protein-Tyrosine Kinases / physiology*
  • Receptors, Growth Factor / physiology
  • Receptors, Metabotropic Glutamate / drug effects
  • Receptors, Metabotropic Glutamate / physiology
  • Receptors, Neurotransmitter / classification
  • Receptors, Neurotransmitter / drug effects
  • Receptors, Neurotransmitter / physiology*
  • Signal Transduction / drug effects
  • Signal Transduction / physiology*
  • Synaptic Transmission / drug effects
  • Synaptic Transmission / physiology
  • Transcriptional Activation
  • Vertebrates / physiology
  • src-Family Kinases / physiology*


  • Nerve Tissue Proteins
  • Neurotransmitter Agents
  • Receptors, Growth Factor
  • Receptors, Metabotropic Glutamate
  • Receptors, Neurotransmitter
  • Receptor Protein-Tyrosine Kinases
  • src-Family Kinases
  • Heterotrimeric GTP-Binding Proteins