ADENOSINE MODULATES CELL-PROLIFERATION IN HUMAN COLONIC ADENOCARCINOMA - I - POSSIBLE INVOLVEMENT OF ADENOSINE A(1) RECEPTOR SUBTYPES IN HT29 CELLS

Several lines of evidence suggest that extracellular adenosine interac ting with specific cell surface receptors may influence cell growth an d differentiation of cancer cells in culture. The data presented here demonstrate that various treatments of human colonic adenocarcinoma HT 29 cells in the presence of exogenously added adenosine deaminase, whi ch converts extracellular adenosine into inosine, resulted in a signif icant decrease of the proliferation. Cell growth inhibition was also o bserved in the presence of adenosine A(1) receptor antagonists. These various treatments also induced a significant elevation of basal intra cellular cAMP levels. This strongly indicated that extracellular adeno sine was maintaining low intracellular cAMP levels in HT29 cells. A pa rtial pharmacological characterization of the binding of the adenosine A(1) receptor agonist [H-3]CCPA (2-chloro-N-6-cyclopentyl[2,3,4,5-H-3 ]aden and the adenosine A(1) receptor antagonist [H-3]DPCPX (cyclopent yl-1,3-dipropyl[2,3-H-3]xanthin to HT29 cells is also provided. Togeth er the data support the idea that A(1)-adenosine receptors are express ed in HT29 cells and might mediate part of the above described effects of adenosine on cell proliferation. (C) 1998 Elsevier Science B.V.