Daily rhythms of P-glycoprotein expression in mice

Recent studies have shown the gene expression of several transporters to be circadian rhythmic. However, it remains to be elucidated whether the expression of P-glycoprotein, which is involved in the transport of many medications, undergoes 24h rhythmicity. To address this issue, we investigated daily profiles of P-glycoprotein mRNA and protein levels in peripheral mouse tissues. In the liver and intestine, but not in the kidney, Abcbla mRNA expression showed clear 24h rhythmicity. On the other hand, Abcb1b and Abcb4, the other P-glycoprotein genes, did not exhibit significant rhythmic expression in the studied tissues. In the intestine, levels of whole P-glycoprotein also exhibited a daily rhythm, with a peak occurring in the latter half of the light phase and it trough at the onset of the light phase. Consistent with the day-night change of P-glycoprotein level, the ex vivo accumulation of digoxin, an Abcbla P-glycoprotein substrate, into the intestinal segments at the onset of dark phase was significantly lower than it was at the onset of the light phase. Thus, Abcbla P-glycoprotein expression, and apparently its function, are 24h rhythmic at least in mouse intestine tissue. This circadian variation might be involved in various chronopharmacological phenomena.