Signal transduction mechanism responsible for changes in axoplasmic transport caused by neurotransmitters.
Transduction mechanism for modulation of axoplasmic transport by neurotransmitters was studied using cultured mouse superior cervical ganglion cells. The transported particles were analyzed with a computer-assisted video-enhanced differential interference contrast microscope system. Acetylcholine depressed and adrenaline increased axoplasmic transport. GTP-binding proteins linked with both receptors activate or inactivate adenylyl cyclase, thereby altering the intracellular concentration of cyclic AMP. The cyclic AMP activates protein kinase A, which phosphorylates certain enzymes and the enzymes in turn phosphorylate motor proteins. An inhibitor protein kinase A, KT5720, decreases the number of the transported particles. In a stable state the cyclic AMP level stays at a normal level. Treatment with neurotransmitters causes a change in this level, which changes the activity of protein kinase A and thus decreases or enhances the phosphorylation of motor proteins. These changes are involved in the modulation of axoplasmic transport.
Takenaka
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T
Department of Physiology, Yokohama City University, Japan.
Kawakami
T
T
D000109:Acetylcholine / Q000494:pharmacology*; D000818:Animals; D001370:Axonal Transport / Q000187:drug effects*; D002227:Carbazoles; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004837:Epinephrine / Q000494:pharmacology*; D019204:GTP-Binding Proteins / Q000378:metabolism; D007211:Indoles / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D018715:Microscopy, Video; D008959:Models, Neurological; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D018377:Neurotransmitter Agents / Q000494:pharmacology*; D010766:Phosphorylation; D011758:Pyrroles / Q000494:pharmacology; D043585:Receptor, Muscarinic M2; D018343:Receptors, Adrenergic, beta-2 / Q000502:physiology; D011976:Receptors, Muscarinic / Q000502:physiology; D015398:Signal Transduction; D017783:Superior Cervical Ganglion / Q000187:drug effects / Q000502:physiology*
D002227:Carbazoles; D004791:Enzyme Inhibitors; D007211:Indoles; D018377:Neurotransmitter Agents; D011758:Pyrroles; D043585:Receptor, Muscarinic M2; D018343:Receptors, Adrenergic, beta-2; D011976:Receptors, Muscarinic; C057416:KT 5720; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D019204:GTP-Binding Proteins; D000109:Acetylcholine; D004837:Epinephrine