A1 adenosine receptor activation inhibits neurite process formation by rhokinase-mediated pathways

A1 adenosine receptors (A1ARs) are expressed in the brain during critical p eriods of neurogenesis and neuronal differentiation. To examine influences of A1AR activation on neuronal development we studied the effects of A1AR a ctivation on process growth in PC12 cells expressing A1ARs and in primary c ultures of cortical and hippocampal neurons. In PC12 cells, we found that A 1AR activation potently inhibited nerve growth factor (NGF)-induced neurite growth and induced stress fiber formation. A1ARs action was not mediated b y 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 A1A R action was also mediated by Rho kinase. These data show that A1AR activat ion inhibits neurite growth and that the inhibitory effects of A1AR are dep endent on Rho kinase. NeuroReport 12:3057-3063 (C) 2001 Lippincott Williams & Wilkins.