BACKGROUND AND PURPOSE:

The function of the endocannabinoid system (ECS) in the renal tissue is not completely understood. Kidney function is closely related to ion reabsorption in the proximal tubule, the nephron segment responsible for the reabsorption of 70- 80% of the filtrate. We studied the effect of compounds modulating the activity of cannabinoid CB receptors on the active reabsorption of Na+ in LLC-PK1 cells.

EXPERIMENTAL APPROACH:

Changes in (Na++K+)-ATPase activity were assessed after treatment with WIN55,212-2 (WIN), a non-selective lipid agonist, and hemopressin (HP), a peptide inverse agonist at CB1 receptors. The signaling pathways involved in the modulation of Na+ transport were investigated with pharmacological tool.

KEY RESULTS:

The mRNAs encoding for enzymes of the ECS are expressed in LLC-PK1 as well as the CB1 and CB2 receptors and TRPV1 channels. WIN (10-7 M) and HP (10-6 M) altered Na+ reabsorption in LLC-PK1 in a dual manner. They both acutely (after 1 min) increased (Na++K+)-ATPase activity in a way attenuated by a TRPV1 antagonist. WIN stimulatory effect persisted until 30 min, when it was attenuated by a CB1 antagonist and by a PKC inhibitor. HP instead inhibited (Na++K+)-ATPase after 30 min incubation, and this effect was attenuated by a CB1 antagonist and a PKA inhibitor CONCLUSION AND IMPLICATIONS: ECS is expressed in LLC-PK1 cells. Both TRPV1 and CB1 regulate (Na++K+)-ATPase activity in these cells, and are modulated by lipid and peptide CB1 ligands, which act via different signaling pathways.
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