Daytime-Dependent Changes of Cannabinoid Receptor Type 1 and Type 2 Expression in Rat Liver.

The present study was performed to investigate the diurnal expression pattern of cannabinoid receptor type 1 (CB₁) and type 2 (CB₂) in liver tissue of 12- and 51-week-old normoglycemic Wistar rats. By using real-time RT-PCR, daytime dependent changes in both age groups and, for both, hepatic Cnr1 and Cnr2 receptor mRNA levels were measured. Highest amount of mRNA was detected in the light period (ZT3, ZT6, and ZT9) while the lowest amount was measured in the dark period (ZT18 and ZT21). Diurnal transcript expression pattern was accompanied by comparable changes of protein level for CB₁, as shown by Western blotting. The current results support the conclusion that expression pattern of cannabinoid receptors are influenced by light/dark cycle and therefore seems to be under the control of a diurnal rhythm. These findings might explain the differences in the efficacy of cannabinoid receptor agonists or antagonists. In addition, investigation of liver of streptozotocin (STZ)-treated 12- and 51-week-old rats show alterations in the diurnal profile of both receptors Cnr1 and Cnr2 compared to that of normoglycemic Wistar rats. This suggests an influence of diabetic state on diurnal expression levels of cannabinoid receptors.