Arachidonic acid release mediated by OX1 orexin receptors.

摘要: Background and purpose:  We have previously shown that lipid mediators, produced by phospholipase D C, are generated in OX1 orexin receptor signalling with high potency, presumably mediate some of the physiological responses to orexin. In this study, we investigated whether ubiquitous A2 (PLA2) system is also involved signalling. Experimental approach:  Recombinant Chinese hamster ovary-K1 cells, expressing human receptors, were used as a model system. Arachidonic acid (AA) release was measured from 3H-AA-labelled cells. Ca2+ assessed using single-cell imaging. Key results:  Orexins strongly stimulated [3H]-AA (maximally 4.4-fold). Orexin-A somewhat more potent than orexin-B (pEC50= 8.90 8.38 respectively). The concentration–response curves appeared biphasic. fully inhibited cPLA2 iPLA2 inhibitor, methyl arachidonyl fluorophosphonate, whereas inhibitors, R- S-bromoenol lactone, caused only partial inhibition. response dependent on influx, inhibitor studies suggested involvement receptor-operated influx pathway. pathway, other hand, partially PLA2 activity. extracellular signal-regulated kinase, but not protein kinase activation at low concentrations. Conclusions implications:  Activation receptors induced strong, high-potency AA release, possibly via multiple species, may be important for influx. coincided messenger responses, interact these signals.