Related Experiment Video
Updated: Aug 16, 2026
07:27
Two-photon Imaging of Microglial Processes' Attraction Toward ATP or Serotonin in Acute Brain Slices
Published on: January 31, 2019
Adenosine A2A receptor stimulation potentiates nitric oxide release by activated microglia
Josep Saura1, Ester Angulo, Aroa Ejarque
1Department of Pharmacology and Toxicology, IIBB, CSIC, IDIBAPS, Barcelona, Spain. jsafat@iibb.csic.es
Journal of Neurochemistry
|August 12, 2005
Summary
Adenosine A2A receptor stimulation enhances neuroinflammation by boosting microglial nitric oxide production. Blocking these receptors may offer neuroprotection by reducing this inflammatory response.
Area of Science:
- Neuroscience
- Immunology
- Pharmacology
Background:
- Adenosine A2A receptors (A2AR) are implicated in neuroprotection when absent or inhibited.
- Glial A2AR activation may contribute to neurodegeneration.
- Understanding glial A2AR function is crucial for developing neuroprotective strategies.
Purpose of the Study:
- To investigate the role of A2AR stimulation in glial cell responses.
- To determine the effects of A2AR activation on glial cells, particularly in the context of inflammation.
- To elucidate the mechanisms underlying A2AR-mediated potentiation of glial inflammatory responses.
Main Methods:
- Primary mouse cortical mixed glial cultures (astrocytes and microglia) were utilized.
- Cells were treated with an A2AR agonist (CGS21680) and/or lipopolysaccharide (LPS).
- Nitric oxide (NO) release, NO synthase-II (NOS2) expression, and A2AR binding were measured.
Main Results:
- A2AR stimulation potentiated LPS-induced NO release and NOS2 expression in a time- and dose-dependent manner.
- This potentiation was blocked by an A2AR antagonist (ZM-241385) and absent in A2AR-deficient mice.
- A2ARs were found on microglia, and their activation required astrocytes for the potentiating effect on NO production.
Conclusions:
- A2AR stimulation exacerbates neuroinflammation by increasing microglial NO production.
- Astrocytes are necessary for A2AR-mediated potentiation of microglial NO release.
- Inhibition of A2ARs may confer neuroprotection by attenuating microglial NO production.
Related Concept Videos
01:28Nitric Oxide Signaling Pathway
Nitric oxide (NO), an inorganic gas, acts as a potent second messenger in most animal and plant tissues. NO diffuses out of the cells that produce it and enters the neighboring cells to generate a downstream response. NO synthase (NOS) catalyzes NO production by the deamination of the amino acid arginine. There are three isoforms of NOS. Endothelial cells have endothelial NOS (eNOS), nerve and muscle cells have neuronal NOS (nNOS), and macrophages produce inducible NOS (iNOS) upon exposure to...
01:31Adrenergic Receptors: ɑ Subtype
Adrenoceptors are classified into α and ꞵ classes based on their potencies to catecholamine agonists. α-adrenoceptors show the following order of catecholamine potency:
Adrenaline ≥ Noradrenaline >> Isoprenaline
α-adrenoceptors are further divided into α1 and α2-adrenoceptors.
α1-Adrenoceptors: These receptors are located postsynaptically on the effector organs and cause constriction of smooth muscle mediated by activation of phospholipase C—inositol-1,4,5-trisphosphate...
Adrenaline ≥ Noradrenaline >> Isoprenaline
α-adrenoceptors are further divided into α1 and α2-adrenoceptors.
α1-Adrenoceptors: These receptors are located postsynaptically on the effector organs and cause constriction of smooth muscle mediated by activation of phospholipase C—inositol-1,4,5-trisphosphate...
01:25Adrenergic Agonists: Indirect-Acting Agents
Indirect-acting adrenergic agonists potentiate the effects of endogenous catecholamines through different mechanisms without directly binding to adrenoceptors.
One mechanism involves depleting stored catecholamines by displacing them from synaptic vesicles. These agents, known as "displacers," are transported into vesicles at the expense of noradrenaline. Examples include amphetamine and tyramine, which lack a catechol moiety, resulting in prolonged action, improved oral bioavailability, and...
One mechanism involves depleting stored catecholamines by displacing them from synaptic vesicles. These agents, known as "displacers," are transported into vesicles at the expense of noradrenaline. Examples include amphetamine and tyramine, which lack a catechol moiety, resulting in prolonged action, improved oral bioavailability, and...
01:23Drugs Acting on Autonomic Ganglia: Stimulants
Ganglionic stimulants activate NM nicotinic receptors in autonomic ganglia, falling into two categories: nicotine mimetics [e.g., lobeline, dimethylpiperazine, tetramethylammonium] and muscarinic receptor agonists [e.g., muscarine, methacholine]. The first category's action is rapid and blocked by nicotinic receptor antagonists, while the second category's action is delayed and blocked by atropine-like agents. Nicotine, an alkaloid, affects the heart rate by stimulating sympathetic or...
01:30Ligand-Gated Ion Channel Receptor: Gating Mechanism
Ligand-gated ion channels are transmembrane proteins that play a vital role in intercellular communication and functions of the nervous system. They allow the influx of ions across the membrane once the neurotransmitter binds, allowing the subsequent transmission of electrical excitation across the neurons. Other ligand-gated ion channels, like the γ-aminobutyric acid (GABA) receptor, permit anions like chloride into the cells on the binding of the GABA molecule. Their entry into the cell...
01:27Adrenergic Neurons: Neurotransmission
Postganglionic sympathetic fibers (except those supplying the sweat glands) releasing noradrenaline or norepinephrine are called noradrenergic or adrenergic neurons. Noradrenaline, dopamine, adrenaline, or epinephrine are collectively called "catecholamines" as they contain a catechol moiety and an amine side chain. The five stages of neurotransmitter release involve their synthesis, storage, release, reuptake and metabolism.
Synthesis: Catecholamine synthesis requires tyrosine, which is taken...
Synthesis: Catecholamine synthesis requires tyrosine, which is taken...