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Phospholipid turnover in isolated rat pancreatic acini. Consideration of the relative roles of phospholipase A2 and phospholipase C.

ABSTRACT: The purpose of the present study was to explore the interaction of phosphatidylinositol breakdown and the turnover of arachidonic acid in isolated rat pancreatic acini by using receptor agonists and the calcium ionophore ionomycin. Acini prelabelled with myo-[(3)H]inositol in vivo responded to carbachol with a rapid breakdown of phosphatidylinositol. In the presence of [(32)P]P(i), carbachol increased labelling of phosphatidic acid and phosphatidylinositol within 1 and 5 min respectively. Carbachol also rapidly stimulated the incorporation of [(14)C]arachidonic acid into phosphatidylinositol within 2 min, and the peptidergic secretagogue caerulein caused the loss of radioactivity from phospholipids prelabelled with arachidonic acid. Ca(2+) deprivation partially impaired the stimulatory action of carbachol on arachidonic acid turnover. In contrast with its stimulatory effects on [(32)P]P(i) and [(14)C]arachidonate incorporation, carbachol inhibited the incorporation of the saturated fatty acid stearic acid into phosphatidylinositol. Whereas ionomycin stimulation of phosphatidylinositol breakdown and [(32)P]P(i) labelling of phospholipids was slower in onset and less effective than carbachol stimulation, the ionophore effectively promoted (arachidonyl) phosphatidylinositol turnover within 2 min. These results implicate two separate pathways for stimulated phosphatidylinositol degradation in the exocrine pancreas, involving phospholipases A(2) and C. Whereas mobilization of cellular Ca(2+) appears sufficient to cause activation of phospholipase A(2) and amylase secretion, additional events triggered by receptor activation may be required to act in concert with Ca(2+) to optimally stimulate phospholipase C. The nature of the interaction between phospholipases A(2) and C and their specific physiological roles in pancreatic secretion remain to be elucidated.

SUBMITTER: Halenda SP

PROVIDER: S-EPMC1154022 | biostudies-other | 1982 Dec

REPOSITORIES: biostudies-other

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Project description:Recent findings have indicated that secreted phospholipases A2 (sPLA2s) have anti-inflammatory functions, including relief of symptoms in a mouse model of mastitis. This prompted us to investigate the therapeutic application of sPLA2, PLA2G1B, for bovine mastitis. Initial testing of PLA2G1B's effect on bovine mammary epithelial cell (bMEC) line PS revealed no changes in cell viability or cytokine-secretion pattern. However, when cells were first treated with lipopolysaccharide endotoxin (LPS) or live bacteria (Escherichia coli or Staphylococcus aureus), incubation with PLA2G1B significantly improved cell viability, suggesting involvement of sPLA2s in protecting membranes from lipid-peroxidation damage, rather than a bactericidal action. When PLA2G1B was applied simultaneously with LPS, a significant short-term reduction in interleukin-8 secretion was observed compared with bMECs treated only with LPS, supporting previous reports that PLA2G1B affects interleukin-8 signaling in similar cells. Following the favorable outcome of the in vitro experiments, we tested PLA2G1B in vivo by mammary infusion into infected glands. In one of a small sample (n = 4) of lactating cows chronically infected with Streptococcus dysgalactiae, a single PLA2G1B treatment completely cleared inflammation and bacteria, demonstrating its potential to cure subclinical mastitis. PLA2G1B treatment did not affect coagulase-negative staphylococci infection. These types of mastitis may involve formation of a resistant biofilm, and its elimination may relate to sPLA2s' characteristic ability to aggregate with cellular debris, facilitating their internalization by macrophages. In a bovine model of clinical mastitis based on introduction of E. coli via the streak canal, a single mammary infusion of PLA2G1B led to faster recovery to pre-infection milk-yield levels and decrease of somatic cell counts. In this case, all of sPLA2s' modes of resolving inflammation may apply, including competitive binding of the sPLA2s' receptor, the inactivation of which confers resistance to endotoxic shock. Hence, this study strongly supports further research into PLA2G1B as a cure for bovine mastitis.

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Phospholipid turnover in isolated rat pancreatic acini. Consideration of the relative roles of phospholipase A2 and phospholipase C.

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