Mobilization of cellular Ca 2+ by lysophospholipids in rat islets of Langerhans

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To determine whether lysophospholipids mobilize cellular Ca 2+, intact rat islets were prelabelled with 45Ca 2+ and subjected to three maneuvers designed to simulate the physiologic accumulation of lysophospholipids: (1) exogenous provision; (2) addition of porcine pancreatic phospholipase A 2; and (3) provision of p-hydroxymercuribenzoic acid, which impedes both the reacylation and hydrolysis of endogenous lysophospholipids, leading to their accumulation in islets. Each maneuver provoked 45Ca 2+ efflux at concentrations nearly identical to those previously reported to induce insulin release in the absence of toxic efffects on the islets. Lysophosphatidylcholine (lysoPC) and lysophosphatidylinositol were active, whereas the ethanolamine and serine derivatives, and lysophosphatidic acid, were much less effective. The effects of lysoPC were reversible; they also were reduced by lanthanum or gentamicin (which are probes of superficial, plasma membrane-bound stores of Ca 2+) or by prior depletion of membrane-bound cellular Ca 2+ stores using ionomycin, but not by removal of extracellular Ca 2+ or Na +. The effects of lysoPC, phospholipase A 2 and p-hydroxymercuribenzoic acid were largely independent of any hydrolysis to, or accumulation of, free fatty acids as assessed by resistance to dantrolene or trifluoperazine (which selectively reduce arachidonic acid-induced 45Ca 2+ efflux and insulin release). Thus, lysophospholipids are a newly recognized class of lipid mediators which may promote insulin release at least in part via mobilization of a pool(s) of Ca 2+ (‘trigger Ca 2+’) bound in the plasma membrane and possibly in other cellular membranes.