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Chronic sustained hypoxia (CSH) alters the function of adenosine A2A receptor in the nucleus of solitary tract (NTS)
Author(s) -
Zhang Weirong,
Mifflin Steve
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.783.7
Subject(s) - solitary tract , cgs 21680 , adenosine , adenosine a1 receptor , adenosine a2a receptor , agonist , receptor , medicine , adenosine receptor , glutamate receptor , endocrinology , extracellular , chemistry , biology , biochemistry
Adenosine modulates cardio‐respiratory activity in the NTS via both A1 and A2A receptors. Normal ambient extracellular ADO primarily activates A1 receptors, which have a higher affinity than A2A receptors. However, A2A receptors may be important when extracellular ADO levels increase during hypoxia. To examine how CSH exposure modulates adenosine A2A receptor function in the NTS, whole‐cell recordings of NTS second‐order neurons identified following DiA labeling of the carotid bodies were obtained in a brainstem slice. We tested the effect of A2A receptor agonist CGS 21680 on spontaneous release of glutamate in NTS slices collected from normoxic rats (NORM) and rats exposed to CSH (10% FIO2 for 7 days) by measuring miniature EPSCs (mEPSCs). CGS 21680 (10 nM) increased the frequency of mEPSCs in both NORM and CSH neurons, but the increase was significantly greater in CSH than in NORM (48±3%, n=5 vs 25±6%, n=6, p<0.01). In addition, 4/5 CSH neurons showed significant increase in the amplitude of mEPSCs (12±4%) while only 1/6 NORM neuron showed increase (8%). The results indicate that activation of adenosine A2A receptors increases pre‐synaptic glutamate release in the NTS. Exposure to CSH enhances A2A receptor‐induced pre‐synaptic glutamate release and induces a de novo, post‐synaptic response. This work is supported by AHA BGIA 0865269F and NIH HL41894.