Nerve growth factor (NGF) expression in rat microglia is induced by adenosine A2a-receptors.
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 A1- and A2-agonist 5'-(N-ethylcarboxamido)-adenosine (NECA) induces an increase in NGF mRNA expression and NGF protein release. Whereas the A1-specific agonist cyclopentyladenosine (CPA) only minimally affected NGF release, the A2a-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 A2a-receptor-sensitive, cAMP-mediated mechanism of microglial NGF synthesis. Our results indicate that A2a-adenosine receptors modulate microglial neurotrophin expression and release.
Heese
K
K
Department of Physiology, University of Basel, Vesalianum, Switzerland.
Fiebich
B L
BL
Bauer
J
J
Otten
U
U
D000241:Adenosine / Q000031:analogs & derivatives / Q000494:pharmacology; D019830:Adenosine-5'-(N-ethylcarboxamide); D000818:Animals; D000831:Animals, Newborn; D000959:Antihypertensive Agents / Q000494:pharmacology; D003994:Bucladesine / Q000494:pharmacology; D005576:Colforsin / Q000494:pharmacology; D015870:Gene Expression / Q000502:physiology; D017628:Microglia / Q000737:chemistry* / Q000378:metabolism; D009414:Nerve Growth Factors / Q000096:biosynthesis / Q000235:genetics*; D010627:Phenethylamines / Q000494:pharmacology; D016133:Polymerase Chain Reaction; D058906:Purinergic P1 Receptor Agonists; D058915:Purinergic P1 Receptor Antagonists; D051381:Rats; D017208:Rats, Wistar; D043705:Receptor, Adenosine A2A; D018047:Receptors, Purinergic P1 / Q000502:physiology*; D014665:Vasodilator Agents / Q000494:pharmacology; D014970:Xanthines / Q000494:pharmacology
D000959:Antihypertensive Agents; D009414:Nerve Growth Factors; D010627:Phenethylamines; D058906:Purinergic P1 Receptor Agonists; D058915:Purinergic P1 Receptor Antagonists; D043705:Receptor, Adenosine A2A; D018047:Receptors, Purinergic P1; D014665:Vasodilator Agents; D014970:Xanthines; C061282:2-(4-(2-carboxyethyl)phenethylamino)-5'-N-ethylcarboxamidoadenosine; C081198:KF 17837; D005576:Colforsin; D019830:Adenosine-5'-(N-ethylcarboxamide); D003994:Bucladesine; C051360:1,3-dipropyl-8-cyclopentylxanthine; D000241:Adenosine