title: The effect of phospholipase A2 on chloride transport by pancreatic secretory granules.
abstract: Secretory granules from the rat pancreas contain electrolyte transport pathways that may contribute to exocrine fluid production. The Cl- selective transport pathway was measured indirectly in isolated granules by ionophore-induced lysis after suspension in isotonic KCl. This Cl- transport was shown to respond to alterations in the granule membrane lipid environment. Exogenously added phospholipase A2 (PLA2) caused an increase of up to 193% in the Cl- specific transport by the isolated granules. In addition, the products of PLA2 hydrolysis, lysophospholipids and unesterified fatty acids, directly increased the rate of Cl- transport when incubated with granules in vitro. Lysophospholipids (2.0 micrograms/ml) increased the Cl- transport between 280-450% (depending on the lysophospholipid species). Similarly, free fatty acids (10 microM) increased the granule Cl- transport from 25% with capric acid (10:0) to 255% with arachidonic acid (20:4). The relative extent of stimulation by fatty acids was dependent on their carbon chain length and to a lesser extent, the degree of unsaturation. The inhibition (68%) of PLA2 promoted granule lysis by 4-acetamido-4'-isothiocyanatostilbene 2,2'-disulfonic acid (0.5 mM) also suggests that the effect is specific for the granule Cl- channel. Thus, the data show that zymogen granule Cl- transport is influenced by membrane lipids and supports a role for PLA2 in controlling electrolyte transport during stimulus-secretion coupling.
authors.affiliation: Department of Biological Sciences, Northern Illinois University, DeKalb 60115-2861.
authors.forename: K W
authors.initials: KW
authors.lastname: Gasser
authors.forename: J R
authors.initials: JR
authors.lastname: Holda
mesh_terms: D000818:Animals; D001692:Biological Transport; D002712:Chlorides / Q000378:metabolism*; D003594:Cytoplasmic Granules / Q000187:drug effects / Q000378:metabolism; D005227:Fatty Acids / Q000378:metabolism / Q000494:pharmacology; D005231:Fatty Acids, Unsaturated / Q000494:pharmacology; D007425:Intracellular Membranes / Q000201:enzymology; D008246:Lysophospholipids / Q000378:metabolism; D008563:Membrane Lipids / Q000378:metabolism; D010179:Pancreas / Q000378:metabolism* / Q000648:ultrastructure; D010741:Phospholipases A / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D054467:Phospholipases A2; D011796:Quinacrine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D002712:Chlorides; D005227:Fatty Acids; D005231:Fatty Acids, Unsaturated; D008246:Lysophospholipids; D008563:Membrane Lipids; D010741:Phospholipases A; D054467:Phospholipases A2; D011796:Quinacrine