Abstract:
:The effects of the basic polypeptide melittin on islet phospholipid degradation and insulin release were studied in static incubations of intact rat islets as a possible model of endogenous phospholipase A2 (PLA2) activation. Melittin (2 micrograms/ml) increased [3H]-arachidonic acid [( 3H]-AA) release from prelabeled islets (at 1.7 mM glucose) to 371% of basal values. Concomitantly, melittin induced degradation of islet phospholipids labeled with [3H]-AA or [14C]-stearic acid, and led to the accumulation of stearate-labeled (but not AA-labeled) lysophosphatidylcholine (LPC, 605% of control). These findings suggested, for the first time in intact rat islets, the presence and activation of a PLA2. Under identical conditions, melittin initiated insulin secretion (at 1.7 mM glucose) in a manner that represented stimulation of physiologic exocytosis--that is, it was dose-dependent, reversible (albeit slowly), unassociated with impairment of other physiologic islet processes (i.e. the response to 16.7 mM glucose after removal of the drug) and inhibitable by reduced ambient temperature. The effect of melittin seemed to be independent of extracellular Ca2+ influx or mobilization of intracellular Ca2+ stores but was blocked by nickel or lanthanum, indirectly suggesting that the effects of this cationic amphiphile might involve a superficial pool of Ca2+. Unexpectedly, melittin-induced insulin release (at least at low glucose concentrations) was not greatly or consistently altered by a battery of inhibitors of endogenous PLA2 or of enzymes affecting AA oxygenation. Furthermore, significant contamination by bee venom PLA2 of the commercially-available melittin preparation was found, and insulin release could be induced by pure bee venom PLA2, probably through the generation of lysophospholipids. Although estimates of the amount of PLA2 in the melittin preparation suggested that such contamination was insufficient to explain at least some of the islet phospholipid hydrolysis and insulin release caused by melittin, we conclude that this agent does not serve as a specific probe of the role of endogenous PLA2 or of AA lipoxygenation in hormone release.
journal_name
Biochem Pharmacoljournal_title
Biochemical pharmacologyauthors
Metz SAdoi
10.1016/0006-2952(86)90438-7subject
Has Abstractpub_date
1986-10-01 00:00:00pages
3371-81issue
19eissn
0006-2952issn
1873-2968pii
0006-2952(86)90438-7journal_volume
35pub_type
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