Influence of derivatives of arachidonic and docosohexaenic acids on AMPA receptors in Purkinje neurons and cognitive functions in mice

Structure–Activity Relationships of Fish Oil Derivatives with Antiallergic Activity in Vitro and in Vivo

“…29 However, surprisingly, the incorporation of the ethanolamide function to the place of the free acid of the fatty acids produced anti-degranulating activity. Comparing C18 fatty acids with ethanolamide (10−12), an omega-9 fatty acid, oleic acid ethanolamide with one double bond (10) had no antidegranulating activity. Ethanolamide of linoleic acid with two double bonds (11), an omega-6 fatty acid, showed weak activity.…”

“…Among omega-3 fatty acids with antiallergic activity found in this study, EPEA and DHEA yielded better activity than ethanolamide of α-linolenic acid. In addition, some studies indicate that DHEA is an important lipid mediator related to a variety of biological functions such as anticancer and anti-inflammation in in vitro and in vivo experiments, − which implies that DHEA derivatives with improved biological activity have a big potential to be used for the treatment of a wide range of DHEA-related disorders including allergy. Thus, DHEA was used as a lead structure for the SARs in this study.…”

“…Studies indicate that fish oil and omega-3 PUFAs possess broad beneficial effects on human health. In vitro and in vivo anti-inflammatory effects of fish oil and omega-3 PUFAs are well addressed by some research groups. , The risk of cancers, cardiovascular disease, hypertension, and neurological disorders is known to be reduced by intake of fish oil or omega-3 PUFAs. − Recently, some studies have revealed that consumed DHA and EPA are endogenously converted to an ethanolamide metabolite, docosahexaenoyl ethanolamide (DHEA), and eicosapentaenoyl ethanolamide (EPEA), respectively, and the amide metabolites lead to the biological functions as a lipid mediator in vitro and in vivo. − ,, This suggests that the endogenous ethanolamide metabolites of DHA and/or EPA are important mediators playing a role in showing their wide beneficial effects in the body and that they have a great potential to be used as pharmaceutical lead structures for the treatment of the omega-3 PUFA-related diseases. On the other hand, it has been also well known that fish oil or omega-3 PUFA intake is associated with allergy protection. − However, little is clear about the mode of the antiallergic effect of fish oil or omega-3 PUFAs.…”

Inhibiting spinal secretory phospholipase A2 after painful nerve root injury attenuates established pain and spinal neuronal hyperexcitability by altering spinal glutamatergic signaling

“…[46][47][48][49] Increases in spinal AA concentration competitively bind to the glutamatebinding pocket of the transporter proteins glutamate aspartate transporter 1 (GLAST1) and glutamate transporter-1 (GLT1), reducing glutamate uptake with glutamate spillover into the extracellular synaptic space. [49][50][51][52] Unlike glutamate transporters, AA and other lipid mediators have not been shown to directly bind to metabotropic or ionotropic glutamate receptors; therefore, altered expression of the metabotropic glutamate receptor 5 (mGluR5), N-methly-d-aspartate receptor 1 (NR1) or glutamate receptor GluR1 53,54 following AA or lipid mediator application may be due to indirect activation via spinal glial glutamate uptake disruption. Both decreased spinal GLT1 and increased spinal mGluR5 accompany pain and spinal neuronal hyperexcitability at day 7 after root injury.…”