Neuronal Platelet-Activating Factor Receptor Signal Transduction Involves a Pertussis Toxin-Sensitive G-Protein |
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Authors: | Clark Gary D Zorumski Charles F McNeil Robert S Happel Leo T Ovella Ty McGuire Shannon Bix Gregory J Swann John W |
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Institution: | (1) Depts. of Pediatrics. Neurology. Neuroscience, The Cain Foundation Laboratories, USA;(2) Depts. of Psychiatry, Baylor College of Medicine, Houston, TX;(3) Anatomy and Neurobiology, Washington University School of Medicine, St. Louis, MO;(4) Dept. of Neurology, Louisiana State University Medical School, New Orleans, LA;(5) Neuroscience, The Cain Foundation Laboratories, USA;(6) Depts. of Pediatrics, The Cain Foundation Laboratories, USA. Neuroscience |
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Abstract: | 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. |
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Keywords: | Platelet-activating factor PAF growth cone collapse axonal growth cone presynaptic nerve terminal miniature excitatory post-synaptic currents (MESCS) synaptic plasticity G-protein metabotropic receptor pertussis toxin |
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