RHC 80267 is a potent and selective inhibitor of diacylglycerol lipase [1].
Diacylglycerol lipase is a key enzyme in the biosynthesis of the endocannabinoid 2-arachidonoylglycerol and catalyzes the hydrolysis of diacylglycerol.
RHC 80267 is a potent and selective diacylglycerol lipase inhibitor. RHC 80267 inhibited canine platelet diglyceride lipase with IC50 value of 4 μM. RHC 80267 inhibited diacylglycerol lipase released from rat and dog platelets. Also, RHC 80267 induced diglyceride accumulation and inhibited fatty acid accumulation [1]. In smooth muscle isolated from the guinea-pig gastric antrum, RHC-80267 (0.3-1 μM) increased slow potential frequency and reduced the refractory period for slow potentials generation evoked by depolarizing stimuli from 8 s to 5 s. Also, RHC-80267 enhanced the frequency of slow potentials increased by acetylcholine (ACh). RHC 80267 increased diacylglycerol accumulation, which then activated PKC. PKC was involved in regulating the frequency of slow potentials [2]. In rat mesenteric artery contracted with either KCl or noradrenaline, RHC-80267 (0.1-10 μM) enhanced acetylcholine-evoked relaxation. In brain homogenate, RHC-80267 inhibited cholinesterase activity with IC50 value of 4 μM in a concentration-dependent way. These results suggested that the enhancement of acetylcholine-evoked responses by RHC-80267 was caused by the inhibition of the cholinesterase activity [3].
References:
[1].? Sutherland CA, Amin D. Relative activities of rat and dog platelet phospholipase A2 and diglyceride lipase. Selective inhibition of diglyceride lipase by RHC 80267. J Biol Chem, 1982, 257(23): 14006-14010.
[2].? Suzuki H, Kito Y, Fukuta H, et al. Effects of RHC-80267, an inhibitor of diacylglycerol lipase, on excitation of circular smooth muscle of the guinea-pig gastric antrum. J Smooth Muscle Res, 2002, 38(6): 153-164.
[3].? Ghisdal P, Vandenberg G, Hamaide MC, et al. The diacylglycerol lipase inhibitor RHC-80267 potentiates the relaxation to acetylcholine in rat mesenteric artery by anti-cholinesterase action. Eur J Pharmacol, 2005, 517(1-2): 97-102.
