Modulatory role of lysophosphatidic acid on opioid receptor binding

Arachidonic acid (AA) and lysophosphatidic acid (LPA) are two important signaling molecules generated by the hydrolysis of membrane phospholipids by the action of phospholipase A2 (PLA2) enzymes. We have previously shown that arachidonic acid affects opioid receptor binding in a negative manner. In the present study, we have investigated the modulatory role of LPA on equilibrium binding of [3H]naloxone to rat brain opioid receptors. The preliminary data demonstrates that LPA at physiological concentrations (100-400 nM) was capable of modulating opioid receptor binding. 100 nM free lysophosphatidic acid concentration stimulates while 200 and 400 nM concentrations inhibit binding. This observation brings the possibility of a cross talking mechanism between opioid and LPA signaling pathways.