A1 adenosine receptor activation inhibits neurite process formation by Rho kinase-mediated pathways.
A1 adenosine receptors (A1ARs) are expressed in the brain during critical periods of neurogenesis and neuronal differentiation. To examine influences of A1AR activation on neuronal development we studied the effects of A1AR activation on process growth in PC12 cells expressing A1ARs and in primary cultures of cortical and hippocampal neurons. In PC12 cells, we found that A1AR activation potently inhibited nerve growth factor (NGF)-induced neurite growth and induced stress fiber formation. A1ARs action was not mediated by inhibition of p44/42 MAP kinase activity, as inhibition of MEK/MAP kinase had no effects on A1AR action. When Rho kinase activity was blocked, A1AR agonists no longer inhibited neurite growth and stress fiber formation was blocked. In neurons, A1AR activation also inhibited process growth, and A1AR action was also mediated by Rho kinase. These data show that A1AR activation inhibits neurite growth and that the inhibitory effects of A1AR are dependent on Rho kinase.
Thevananther
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Department of Pediatrics, P.O. Box 208081, Yale University School of Medicine, New Haven, CT 06520, USA.
Rivera
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Rivkees
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D000818:Animals; D001921:Brain / Q000166:cytology / Q000196:embryology* / Q000201:enzymology; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology*; D003599:Cytoskeleton / Q000187:drug effects / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects / Q000502:physiology; D020439:Growth Cones / Q000187:drug effects / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins; D020928:Mitogen-Activated Protein Kinases / Q000187:drug effects / Q000378:metabolism; D020932:Nerve Growth Factor / Q000494:pharmacology; D016501:Neurites / Q000187:drug effects / Q000201:enzymology* / Q000648:ultrastructure; D016716:PC12 Cells / Q000166:cytology / Q000187:drug effects / Q000201:enzymology; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D017434:Protein Structure, Tertiary / Q000235:genetics; D011869:Radioligand Assay; D051381:Rats; D018047:Receptors, Purinergic P1 / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D054460:rho-Associated Kinases
D004791:Enzyme Inhibitors; D047908:Intracellular Signaling Peptides and Proteins; D018047:Receptors, Purinergic P1; D020932:Nerve Growth Factor; D017346:Protein Serine-Threonine Kinases; D054460:rho-Associated Kinases; D020928:Mitogen-Activated Protein Kinases