Nerve growth factor (NGF) expression in rat microglia is induced by adenosine A 2a-receptors

Abstract

Microglial response to stimuli is characterized by secretion of both neurotoxic and neurotrophic factors. Various adenosine receptor agonists stimulated the production of nerve growth factor (NGF) in microglia. Using reverse transcription-polymerase chain reaction (RT-PCR)- and ELISA-techniques, we show that the mixed A 1- and A 2-agonist 5′-( N-ethylcarboxamido)-adenosine (NECA) induces an increase in NGF mRNA expression and NGF protein release. Whereas the A 1-specific agonist cyclopentyladenosine (CPA) only minimally affected NGF release, the A 2a-specific agonist CGS-21680 triggered the greatest increase in microglial NGF synthesis. Analyzing the selective antagonist (E)-8-(3,4-dimethoxystyryl)-1,3-dipropyl-7-methylxanthine (EXIP), as well as modulators of the cyclic AMP (cAMP) pathway, we identified an adenosine A 2a-receptor-sensitive, cAMP-mediated mechanism of microglial NGF synthesis. Our results indicate that A 2a-adenosine receptors modulate microglial neurotrophin expression and release.