Regulation of intracellular calcium release channel function by arachidonic acid and leukotriene B4.

Arachidonic acid has been shown to affect the intracellular calcium concentration in many cell types (1-5), but the target of this regulation was unclear. Here we show that two types of intracellular calcium release channel, the inositol 1,4,5-trisphosphate-gated channel (IP3R) and the ryanodine receptor (RyR) are modulated in an opposing manner by arachidonic acid and its product leukotriene B4 (LTB4). The IP3R was inhibited by arachidonic acid (Ki = 27 nM), whereas the RyR was unaffected by this compound. In contrast, 100 nM LTB4 fully activated the RyR but did not influence the IP3R. The concerted action of arachidonic acid and LTB4 could provide specific mobilization of stored calcium by terminating IP3-induced release and activating the RyR/calcium release channel by its newly identified agonist.