Question: 

In this study the efficacy of Dopamine (DA) and its derivative N-octanoyl-dopamine (NOD) were compared regarding the improvement of renal function and the inhibition of inflammation of ischemia induced acute renal failure (ARF). As a N-acyl-dopamine derivative, we further investigated whether NOD may directly activate the capsaicin receptor TRPV1 using the calcium imaging technique.

Methodology: 

Acutely dissociated rat dorsal root ganglion neurons (DRG) and HEK293-TRPV1 cells were activated repetitively with 30 mM NOD and blocked with the competitive antagonist capsazepine (CPZ, 10 mM). Lewis rats were treated with equimolar concentrations of DA or NOD one hour before and immediately after renal artery clamping for 45 minutes. Renal function and inflammation were assessed at different time-points after induction of ARF.

Results: 

About half of the capsaicin-sensitive DRG neurons and almost all HEK293-TRPV1 cells displayed a significant calcium increase to application of NOD. These responses showed tachyphylaxis and were reduced by CPZ. In contrast DA up to 1 mM did not activate HEK293-TRPV1 cells. NOD significantly improved renal function in ARF compared to DA and saline controls without affecting the mean arterial pressure. Immunohistochemistry revealed a reduced number of monocytes in renal tissue of DA- and NOD-treated rats.

Conclusion: 

Our study demonstrates that NOD is an agonist at TRPV1 although less effective than capsaicin. NOD but not DA mitigates deterioration in renal function after ARF; both display limited anti-inflammatory properties. The beneficial action of NOD on kidney function may - at least in part - be explained by activation and/or desensitization of TRPV1.