Mobilization of cellular Ca2+ by lysophospholipids in rat islets of Langerhans.
To determine whether lysophospholipids mobilize cellular Ca2+, intact rat islets were prelabelled with 45Ca2+ and subjected to three maneuvers designed to simulate the physiologic accumulation of lysophospholipids: (1) exogenous provision; (2) addition of porcine pancreatic phospholipase A2; 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 45Ca2+ efflux at concentrations nearly identical to those previously reported to induce insulin release in the absence of toxic effects 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 Ca2+) or by prior depletion of membrane-bound cellular Ca2+ stores using ionomycin, but not by removal of extracellular Ca2+ or Na+. The effects of lysoPC, phospholipase A2 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 45Ca2+ 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 Ca2+ ('trigger Ca2+') bound in the plasma membrane and possibly in other cellular membranes.
Metz
S A
SA
Research Service, Denver Veterans Administration Medical Center, CO.
D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002118:Calcium / Q000378:metabolism*; D004987:Ethers / Q000494:pharmacology; D005230:Fatty Acids, Nonesterified / Q000096:biosynthesis; D005839:Gentamicins / Q000494:pharmacology; D005947:Glucose / Q000494:pharmacology; D006902:Hydroxymercuribenzoates / Q000494:pharmacology; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D015759:Ionomycin; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism*; D007811:Lanthanum / Q000494:pharmacology; D008246:Lysophospholipids / Q000494:pharmacology*; D008297:Male; D010741:Phospholipases A / Q000494:pharmacology; D054467:Phospholipases A2; D051381:Rats; D011919:Rats, Inbred Strains
D004987:Ethers; D005230:Fatty Acids, Nonesterified; D005839:Gentamicins; D006902:Hydroxymercuribenzoates; D007328:Insulin; D008246:Lysophospholipids; C030601:4-hydroxymercuribenzoate; D015759:Ionomycin; D007811:Lanthanum; D010741:Phospholipases A; D054467:Phospholipases A2; D005947:Glucose; D002118:Calcium