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Title: N-COUMAROYLDOPAMINE AND N-CAFFEOYLDEPAMINE INCREASE CAMP VIA BETA 2-ADRENOCEPTORS IN MYCLOCYTIC U937 CELLS

Author
item Park, Jae

Submitted to: Federation of American Societies for Experimental Biology Conference
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 12/3/2004
Publication Date: 1/10/2005
Citation: Park, J.B. 2005. N-coumaroyldopamine and n-caffeoyldepamine increase camp via beta 2-adrenoceptors in myelocytic U937 cells. Federation of American Societies for Experimental Biology Journal. 19:497-502.

Interpretive Summary: Phytochemicals are important diet components with various health effects on human diseases such as obesity, diabetes, heart diseases, and cancers. Lately, a great deal of research effort has been made to explore how phytochemicals affect adrenoceptors because of their involvement in important biological functions related to human health, i.e., cardio-vascular, pulmonary, and metabolic. In this report, N-caffeoyldopamine and its natural analogues were synthesized and investigated to determine their potency as beta-adrenoceptors in human cells because their chemical structures are strikingly similar to beta adrenoceptor agonists such as dobutamine and denopamine. Among the phytochemicals tested in this study, N-coumaroyldopamine and N-caffeoyldopamine were two most potent compounds, able to increase cAMP at the concentrations lower than 0.05 microM in U937 cells. The outcomes of current and on-going studies will provide researchers in nutrition, molecular biology, and medicine with novel information regarding their suitability as dietary factors for reducing the risks of human chronic diseases such as cardio-vascular illness and pulmonary dysfunction.

Technical Abstract: N-caffeoyldopamine is a phytochemical found in various plants, including cocoa (Theobroma cacao L.). In this paper, N-caffeoyldopamine and its natural analogues (N-cinnamoyldopamine, N-coumaroyldopamine, N-feruloyldopamine, and N-sinapoyldopamine) were synthesized and investigated to determine their potency as beta-adrenoceptor agonists, because they have chemical structures strikingly similar to beta-adrenoceptor agonists. Among the compounds tested in this study, N-coumaroyldopamine and N-caffeoyldopamine were the two most potent compounds, able to increase cAMP at concentrations lower than 0.05 microM in U937 cells. The decreasing order of potency was N-coumaroyldopamine > N-caffeoyldopamine > N-feruloyldopamine > N-sinapoyldopamine > N-cinnamoyldopamine. Using beta-2 specific antagonists (butoxamine and ICI 118551), N-coumaroyldopamine and N-caffeoyldopamine were found to increase cAMP via beta-2 adrenoceptors in U937 cells. In producing cAMP in U937 cells, N-coumaroyldopamine and N-caffeoyldopamine were as potent as several well-known beta-2 adrenoceptor agonists (salbutamol, procaterol, and fenoterol). These results indicate that N-coumaroyldopamine and N-caffeoyldopamine are potent compounds able to increase cAMP via beta-2 adrenoceptors in U937 cells, and they may have potential effects on human health.