Premium
Differential regulation of oxidant generation and [Ca2+]i mobilization by adenosine A1 and A3 receptors in brain astrocytes
Author(s) -
Gebremedhin Debebe,
Jacobs Jesse,
Zhang David,
Rau Nicole,
Harder David R.
Publication year - 2012
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.26.1_supplement.1137.7
Subject(s) - superoxide , agonist , adenosine , adenosine a3 receptor , receptor , stimulation , adenosine a1 receptor , chemistry , adenosine receptor , medicine , receptor antagonist , antagonist , endocrinology , pharmacology , biology , biochemistry , enzyme
Adenosine exerts its effects through 4 types of G‐protein‐coupled receptors, A1, A2a, A2b and A3. The functions of A1 and A3 receptors with regards to superoxide generation and Ca2+ mobilization in brain astrocytes is unknown. We investigated the effects of adenosine A1 and A3 receptors on superoxide generation and Ca2+ mobilization in cultured astrocytes. Stimulation of the A1 receptor with the adenosine A1 agonist N6‐CPA (100 nM) decreased basal superoxide level, whereas stimulation of the A3 receptor with the A3 agonist IB‐MECA (100 nM) increased superoxide production. Pretreatment with A1 receptor antagonist DPCPX (100 nM) rendered the A1 agonist to increase superoxide production, whereas the A3 antagonist MRS‐1220 (100 nM) reduced the A3 stimulated increased superoxide production. As to the effect on [Ca2+ ]i mobilization stimulation of A1 adenosine receptor with N6‐CPA 100 nM caused moderate increase in [Ca2+]i level that was exaggerated following antagonism of the A1 receptor with DPCPX, 100 nM. In contrast, stimulation of the A3 adenosine receptor with IB‐MECA (100 nM) induced a profound increase in [Ca2+]i level that was attenuated by the A3 antagonist MRS‐1220 (100 nM). These findings indicate that modulation of adenosine A1 and A3 receptors impose differential superoxide production and [Ca2+]i mobilization actions in cultured astrocytes that could be protective or injurious.