Anandamide and its metabolites what are their roles in the kidney

Abstract

Anandamide (AEA) is the N-acyl ethanolamide of arachidonic acid, an agonist of cannabinoid and non-cannabinoid receptors in the body. The kidneys are enriched in AEA and in enzymes that metabolize AEA, but the roles of AEA and its metabolites in the kidney remain poorly understood. This system likely is involved in the regulation of renal blood flow and hemodynamics and of tubular sodium and fluid reabsorption. It may act as a neuromodulator of the renal sympathetic nervous system. AEA and its cyclooxygenase-2 metabolites, the prostamides, in the renal medulla may represent a unique antihypertensive system involved in the long-term control of blood pressure. AEA and its metabolites are also implicated as modulators of inflammation and mediators of signaling in inflammation. AEA and its metabolites may be influential in chronic kidney disease states associated with inflammation and cardiovascular diseases associated with hyperhomocysteinemia. The current knowledge of the roles of AEA and its derivatives highlights the need for further research to define and potentially exploit the role of this endocannabinoid system in the kidney.

Potential application of endocannabinoid system agents in neuropsychiatric and neurodegenerative diseases—focusing on FAAH/MAGL inhibitors

“…Two representative endocannabinoids that are widely distributed throughout the central nervous system, N-arachidonoyl-ethanolamine, called anandamide (AEA), and 2-arachidonoyl-glycerol (2-AG), were identified in the pig brain and canine gut [ 11 ], respectively. The kidneys are known to be enriched in AEA and enzymes that metabolize AEA, which are associated with many different physiological and pathophysiological functions, including the regulation of sensory and autonomic nerve signals, the regulation of energy expenditure and balance, and the initiation and control of inflammation [ 12 ]. The detection of 2-AG in the CNS has garnered extensive attention from scholars.…”

The role of cannabinoid signaling in acute and chronic kidney diseases

“…Therefore, the ECS is likely involved in the regulation of renal blood flow and may also play a role in sodium reabsorption at the tubular level. 9 The ECS in models of kidney diseases Early studies have explored the possibility that the beneficial effects of CB1R blockade on metabolism would result in Figure 1 | Cannabinoid receptor types 1 and 2 (CB1R and CB2R) ligands and signaling pathways. (a) CB1R and CB2R share ligands (AEA, 2-AG) and signaling pathways because they are both coupled through G i/o proteins, negatively to adenylate cyclase (AC) and positively to mitogen-activated protein kinases (MAPK).…”

Redox system and phospholipid metabolism in the kidney of hypertensive rats after FAAH inhibitor URB597 administration

“…Anandamide and 2-arachidonoylglycerol (2-AG), ligands of G protein–coupled receptors (mainly CB1/2 and TRPV1), are synthesized on demand from phospholipid arachidonic acid [8] . Endocannabinoids system, mainly endocannabinoids and enzymes metabolizing them, likely is involved in the regulation of renal blood flow and hemodynamics and of tubular sodium and fluid reabsorption but also participates in modulation inflammation and redox balance [11] . It is known that cannabinoid receptors take part in the regulation of redox balance as follows: CB1 activation enhances oxidative stress and may promote tissue injury by enhanced inflammation, MAPK activation, and cell death, while CB2 and TRPV1 activation prevents ROS generation and may play a protective role in preventing renal injuries, possibly by inhibiting the inflammatory response and endothelial cell activation e.g.…”