Phospholipase A2 activation by melittin causes amylase release from exocrine pancreas.
Phospholipase A2-induced deacylation of membrane phospholipids is associated with changes in membrane fluidity. The importance of this reaction in the pancreatic amylase secretory process was tested using melittin, a phospholipase A2 stimulating peptide. Phospholipase A2 activity (using [3H]arachidonic acid release as an index) and amylase secretion were both increased in a time- and concentration-dependent manner by melittin. Phospholipids prelabelled with [3H]oleic acid or [14C]linoleic acid also released radioactive free fatty acids in response to melittin. Prostaglandin synthesis was not involved in the melittin response, since inhibitors of arachidonic acid oxidation (indomethacin, 5,8,11,14-eicosatetraynoic acid) did not alter the ability of melittin to release [3H]arachidonic acid or amylase. When melittin was co-applied with carbachol, cholecystokinin octapeptide, or vasoactive intestinal peptide, amylase secretion was additive. The effect of melittin on both fatty acid and amylase release was dependent on extracellular calcium, though melittin's effects were not dependent on the intracellular accumulation of second messengers such as calcium or cAMP. The data suggest that activation of phospholipase A2 by melittin results in the triggering of the secretory process in exocrine pancreas by a different mechanism than that for other pancreatic secretagogues.
Heisler
S
S
Unité de Biorégulation cellulaire, Le Centre hospitalier de l'Université Laval, Sainte-Foy, Québec, Canada.
D000681:Amylases / Q000378:metabolism*; D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism; D001514:Bee Venoms / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D002132:Calcium Radioisotopes; D002766:Cholecystokinin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D066298:In Vitro Techniques; D007202:Indicators and Reagents; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D015289:Leukotrienes / Q000096:biosynthesis; D008555:Melitten / Q000494:pharmacology*; D010179:Pancreas / Q000166:cytology / Q000187:drug effects / Q000201:enzymology*; D010740:Phospholipases / Q000378:metabolism*; D010741:Phospholipases A / Q000037:antagonists & inhibitors / Q000378:metabolism*; D054467:Phospholipases A2; D011448:Prostaglandin Antagonists / Q000494:pharmacology; D051381:Rats
D001095:Arachidonic Acids; D001514:Bee Venoms; D002132:Calcium Radioisotopes; D007202:Indicators and Reagents; D015289:Leukotrienes; D011448:Prostaglandin Antagonists; D008555:Melitten; D016718:Arachidonic Acid; D002766:Cholecystokinin; D000242:Cyclic AMP; D007770:L-Lactate Dehydrogenase; D010740:Phospholipases; D010741:Phospholipases A; D054467:Phospholipases A2; D000681:Amylases; D002118:Calcium