Submitted to: Book Chapter
Publication Type: Book / chapter
Publication Acceptance Date: 2/20/2001
Publication Date: 4/1/2002
Citation: Jacobson, K.A., Moro, S., Manthey, J.A., West, P.L., Ji, X.-D. Interactions of flavones and other phytochemicals with adenosine receptors. Buslig, B.S., Manthey, J.A., editors. Kluwer Academic/Plenum Publishers, New York, NY. Flavonoids in Cell Function. 2002. p. 163-172. Interpretive Summary: The binding of adenosine, a naturally occurring compound in the human body, to specific receptors, helps influence normal functions of the human body. Adenosine binding influences cardiovascular functions, critical events involving the nervous system, and the immune system. It is observed that certain food components, including a class of compounds termed the flavonoids, can also bind to the adenosine receptors. Hence, these food constituents might influence normal physiological processes that are usually controlled by endogenous levels of adenosine. A class of flavonoids occurring in citrus, termed the polymethoxylated flavones, were observed to bind tightly to the main adenosine receptors. It is possible, therefore, that these compounds may exert biological activity attributable to these binding properties. Further research into these binding properties of these citrus compounds is warranted.
Technical Abstract: Adenosine receptors are involved in the homeostasis of the immune, cardiovascular, and central nervous systems, and adenosine agonists/ antagonists exert many similar effects. The affinity of flavonoids to adenosine receptors suggests that a wide range of natural substances in the diet may potentially block the effects of endogenous adenosine. A competitive radioligand binding assay was developed to screen flavonoid binding to the three main types (A1, A2A, A3) of adenosine receptors. Numerous flavonoids were shown to selectively bind to the different classes of receptors, and structure/activity relationships were built for each. The citrus polymethoxylated flavones exhibited tight binding to the A1 and A2A receptors. Two compounds, 5,7,3',4'-tetramethylquercetin and sinensetin, exhibited the strongest binding to the A3 receptor of all currently tested flavones. This binding to adenosine receptors provides insight into potential modes of action of these citrus flavonoids.