Effects of adenosine A₁ receptor agonists with different residence times on intestinal ischemia reperfusion

Objective To investigate the effect of drug target residence time (RT) of adenosine A₁ receptor agonists on intestinal ischemia reperfusion.

Methods Human colon cancer cell line Caco-2 was cultured in vitro to establish an oxygen glucose deprivation/reoxygenation (OGD/R) model. Before OGD/R, adenosine A₁ receptor agonists (CPA and LUF6941) with different RTs were added to the cells. Cell survival and viability were measured using PI reagents and CCK-8. Western blot assay was used to detect the expression of PI3K and the level of Akt phosphate in the cells.

Results During OGD/R of intestinal cells, CPA and LUF6941 could reduce the rate of apoptosis (P ＜ 0.05 and P ＜ 0.01) and enhance cell viability (P ＜ 0.05 and P ＜ 0.001), while CPA and LUF6941 could increase the expression of PI3K (P ＜ 0.01) and promote the phosphorylation of Akt (P ＜ 0.01); At the same time, the pharmacological effect of LUF6941 with long RT was stronger than that of CPA with short RT (P ＜ 0.05).

Conclusion During OGD/R in intestinal cells, adenosine A₁ receptor agonists with different RTs can reduce apoptosis and enhance cell viability by activating the PI3K/Akt signaling pathway. Agonists with longer RT have stronger pharmacological effects.