25. Adenosine impairs locomotor activity and food intake via the A2A/PKA/KATP channel-dependent activation of caspase 1
| Autor: | Gregory G. Freund, J.P. Walsh, K.A. Kwakwa, P.T. Darmody, G.S. Chiu |
|---|---|
| Rok vydání: | 2013 |
| Předmět: |
medicine.medical_specialty
Endocrine and Autonomic Systems Chemistry Activator (genetics) Immunology Caspase 1 Adenosine A2A receptor Inflammasome Purinergic signalling Pharmacology Adenosine A3 receptor Adenosine Behavioral Neuroscience Adenosine A1 receptor Endocrinology Internal medicine medicine medicine.drug |
| Zdroj: | Brain, Behavior, and Immunity. 32:e7-e8 |
| ISSN: | 0889-1591 |
| DOI: | 10.1016/j.bbi.2013.07.037 |
| Popis: | Adenosine is a neuroimmune regulator that is released during times of cellular stress and damage. Extracellular adenosine can activate caspase 1 and subsequently promote behavioral abnormalities. In this study, mice injected with adenosine displayed depressed locomotor activity and anorexia, while IL-1r1 knockout mice were protected against adenosine-induced maladies. Coadministration of adenosine A2A receptor antagonist (8-(3-Chlorostyryl)-caffeine) as well as A2A genetic knockout mice showed no adenosine dependent activation of caspase 1. Mice treated with adenosine displayed an increase in PKA activity, while the irreversible PKA inhibitor (KT 5720) also protected against caspase 1 upregulation. Prevention of potassium efflux by administration of the sulfonylurea, glyburide, or increasing extracellular potassium concentration also prevented adenosine-induced caspase 1 activation. Finally, when compared to ATP, a classically known activator of the inflammasome, we see that adenosine and ATP both activate caspase 1, but in two separate signaling pathways. Taken together, our data suggest that the activation of the A2A receptor stimulates PKA to illicit potassium efflux via the KATP channel and upregulate caspsae 1 activity. |
| Databáze: | OpenAIRE |
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