Neuronal platelet-activating factor receptor signal transduction involves a pertussis toxin-sensitive G-protein.
In most nonneural systems, platelet-activating factor (PAF) receptor effects are mediated by G-proteins that are often pertussis toxin-sensitive. The activation of pertussis toxin-sensitive G-proteins linked to PAF receptors results in the mobilization of intracellular calcium, at least in part, through the second messenger inositol triphosphate. We have sought to determine if a pertussis toxin-sensitive G-protein is involved in the PAF receptor-mediated phenomena of growth cone collapse and of synaptic enhancement in primary neuronal culture. Using infrared differential interference contrast microscopy and patch-clamp recording techniques, pertussis toxin, but not the inactive B oligomer of the toxin, was found to block both the growth cone collapse and the enhanced synaptic release of excitatory transmitter induced by a nonhydrolyzable PAF receptor agonist, making it likely that Go, Gq, or Gi is the G-protein transducer of PAF receptors in primary neurons. We believe that PAF acts directly on neuronal receptors, which are linked to pertussis toxin-sensitive G-proteins, on the tips of developing neurites, and on presynaptic nerve terminals, leading to growth cone collapse and enhanced synaptic release of transmitter.
Clark
G D
GD
The Cain Foundation Laboratories, Baylor College of Medicine, Houston, TX, USA. gclark@bcm.tmc.edu
Zorumski
C F
CF
McNeil
R S
RS
Happel
L T
LT
Ovella
T
T
McGuire
S
S
Bix
G J
GJ
Swann
J W
JW
D000818:Animals; D000831:Animals, Newborn; D019204:GTP-Binding Proteins / Q000502:physiology*; D020439:Growth Cones / Q000187:drug effects / Q000502:physiology / Q000648:ultrastructure; D006624:Hippocampus / Q000166:cytology / Q000502:physiology*; D007700:Kinetics; D016501:Neurites / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D018408:Patch-Clamp Techniques; D037342:Pertussis Toxin; D010972:Platelet Activating Factor / Q000494:pharmacology; D010980:Platelet Membrane Glycoproteins / Q000502:physiology*; D051381:Rats; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D013569:Synapses / Q000187:drug effects / Q000502:physiology; D010566:Virulence Factors, Bordetella / Q000494:pharmacology*
D010972:Platelet Activating Factor; D010980:Platelet Membrane Glycoproteins; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D010566:Virulence Factors, Bordetella; C039351:platelet activating factor receptor; D037342:Pertussis Toxin; D019204:GTP-Binding Proteins