2-arachidonoylglyceol metabolism is modulated by cannabinoid receptor ligands and by phototransduction related protein in retinal rod outer segments

CHAMORRO AGUIRRE, E.; GAVEGLIO, V.L.; PASCUAL, A.C.; PASQUARÉ, S.J.

Mar del Plata

Congreso; Reunión conjunta SAIC SAI&FAIC SAFIS 2022 - LXVII Reunión Anual de la de la Sociedad Argentina de Investigación Clínica (SAIC); 2022

The endocannabinoid 2-arachidonoylglycerol (2-AG) level in the central nervous system is regulated mainly by diacylglycerol- and monoacylglycerol-lipase (DAGL and MAGL) activities. Lysophosphatidate phosphohydrolase (LPAP) could also generate 2-AG from 2-arachinodonoyl lysophosphatidate. Previous studies demonstrated that MAGL activity is modified in rod outer segment (ROS) membranes treated with buffers of low (5 mM Tris-HCl) or moderate (100 mM Tris-HCl) ionic strength, which mostly extract rhodopsin kinase (RK) and arrestin (Arr), both being proteins related to the phototransduction process. One aim of this work was to analyze if cannabinoid receptor ligands WIN55212-2 (WIN), JWH-133 (JWH), SR141716 (SR1) and SR144528 (SR2) modulate these enzymatic activities in ROS isolated from dark-adapted bovine retinas and exposed to light (3000 lux, ROS B) or kept under darkness (ROS O) for 30 min at 37 °C. Thus, ROS O/B were incubated with cannabinoid ligands for 10 min before adding the radiolabeled substrate. It was observed that WIN and JWH agonists (5 µM) diminished MAG production from LPA by 32% and 60% in ROS O and ROS B, respectively. SR1 and SR2 antagonists (1 µM) also generated a MAG diminution of 71% and 51% in ROS O, respectively, while both antagonists diminished it by 48% in ROS B (n=5, p