A(1) and A(3) adenosine receptors alter glutathione status in an organ-specific manner and influence the changes after inhibition of gamma-glutamylcysteine ligase.
Adenosine levels are increased in stress and act as anti-oxidant and anti-inflammatory mediators by binding to 4 G-protein-coupled receptors. Using genetically modified mice lacking A(1) and A(3) adenosine receptors, treated with ip buthionine-[S,R]-sulphoximine injections to inhibit gamma-glutamylcysteine ligase, the question was addressed whether these receptors modulate the responses to the stress related to altered glutathione levels. This study determined organ glutathione levels and expression of two sub-units of gamma-glutamylcysteine ligase and the cationic x(c)-transporter and found that deletion of one or both adenosine receptors influenced the responses in an organ-specific manner. The lack of A(1) and A(3) adenosine receptors is related to decreased basal glutathione content and down-regulation of gamma-glutamylcysteine ligase sub-units in several organs. Moreover, responses to buthionine-[S,R]-sulphoximine were different. For example, the lack of A(3) adenosine receptors, or their blockade of A(3) by MRS 1191, caused a marked increase in gene expression, which was not observed in mice lacking both A(1) and A(3) receptors. The results indicate that A(1) and A(3) adenosine receptors play a role in antioxidant responses and their role differs in an organ-specific way.
Conte
Carmela
C
Dipartimento di Medicina Sperimentale e Scienze Biochimiche, Università degli Studi di Perugia, Italy.
Grottelli
Silvia
S
Prudenzi
Elvira
E
Bellezza
Ilaria
I
Fredholm
Bertil B
BB
Minelli
Alba
A
D058918:Adenosine A3 Receptor Antagonists; D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D019328:Buthionine Sulfoximine / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D015870:Gene Expression; D005721:Glutamate-Cysteine Ligase / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D005978:Glutathione / Q000235:genetics / Q000378:metabolism*; D008168:Lung / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009928:Organ Specificity; D043682:Receptor, Adenosine A1 / Q000235:genetics / Q000378:metabolism*; D043684:Receptor, Adenosine A3 / Q000235:genetics / Q000378:metabolism*
D058918:Adenosine A3 Receptor Antagonists; D000975:Antioxidants; D004791:Enzyme Inhibitors; D043682:Receptor, Adenosine A1; D043684:Receptor, Adenosine A3; D019328:Buthionine Sulfoximine; D005721:Glutamate-Cysteine Ligase; D005978:Glutathione