Effects of a choline-deficient ethionine-supplemented diet on phospholipase C activity in mouse pancreatic acinar cell membranes and in electropermeabilized mouse pancreatic acini

U. Leli, Ashok Saluja, L. Picard, A. Zavertnik, M. L. Steer

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3 Citations (Scopus)

Abstract

The nonhydrolyzable guanyl nucleotide GTPγS stimulated phosphoinositidase C activity in two preparations obtained from mouse pancreatic acini labeled with myo[2-3H]inositol: a cell-free membrane fraction and intact electropermeabilized acini. This action was dose-dependent, was shared by other nonhydrolyzable guanyl nucleotides such as GMP-phencyclidine hydrochloride and GMP-PMP, as well as by fluoride, and was calcium-independent. Contrarily, no effect was observed even at doses of GTPγS as high as 10 μM when the same protocol was repeated on identical acinar preparations from mice fed a choline-deficient, ethionine-supplemented diet. This regiment is known to uncouple secretagogue-receptor occupancy from inositol 1,4,5-trisphosphate generation in pancreatic acinar cells and lead to necrotizing hemorrhagic pancreatitis. These data lead us to conclude that the ethionine-induced inactivation of guanyl nucleotide-dependent pancreatic phosphoinositidase C in pancreatic acinar cells is not the result of either a decrease in GTP level or a decrease in GTP availability. These findings further confirm previous work from this laboratory, which has shown that the biochemical lesion induced by this diet occurs after the agonist-receptor binding step. The diet-induced lesion could be either at the level of the G-protein that couples the enzyme with the receptor or at the level of the phospholipase itself.

Original languageEnglish (US)
Pages (from-to)847-850
Number of pages4
JournalJournal of Pharmacology and Experimental Therapeutics
Volume253
Issue number2
StatePublished - Jan 1 1990
Externally publishedYes

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Ethionine
Acinar Cells
Type C Phospholipases
Choline
Nucleotides
Cell Membrane
Diet
Guanosine Triphosphate
Calcium Fluoride
Inositol 1,4,5-Trisphosphate Receptors
Phencyclidine
Phospholipases
Inositol
GTP-Binding Proteins
Pancreatitis
Enzymes
glycerophosphoinositol glycerophosphodiesterase

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology

Cite this

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title = "Effects of a choline-deficient ethionine-supplemented diet on phospholipase C activity in mouse pancreatic acinar cell membranes and in electropermeabilized mouse pancreatic acini",
abstract = "The nonhydrolyzable guanyl nucleotide GTPγS stimulated phosphoinositidase C activity in two preparations obtained from mouse pancreatic acini labeled with myo[2-3H]inositol: a cell-free membrane fraction and intact electropermeabilized acini. This action was dose-dependent, was shared by other nonhydrolyzable guanyl nucleotides such as GMP-phencyclidine hydrochloride and GMP-PMP, as well as by fluoride, and was calcium-independent. Contrarily, no effect was observed even at doses of GTPγS as high as 10 μM when the same protocol was repeated on identical acinar preparations from mice fed a choline-deficient, ethionine-supplemented diet. This regiment is known to uncouple secretagogue-receptor occupancy from inositol 1,4,5-trisphosphate generation in pancreatic acinar cells and lead to necrotizing hemorrhagic pancreatitis. These data lead us to conclude that the ethionine-induced inactivation of guanyl nucleotide-dependent pancreatic phosphoinositidase C in pancreatic acinar cells is not the result of either a decrease in GTP level or a decrease in GTP availability. These findings further confirm previous work from this laboratory, which has shown that the biochemical lesion induced by this diet occurs after the agonist-receptor binding step. The diet-induced lesion could be either at the level of the G-protein that couples the enzyme with the receptor or at the level of the phospholipase itself.",
author = "U. Leli and Ashok Saluja and L. Picard and A. Zavertnik and Steer, {M. L.}",
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T1 - Effects of a choline-deficient ethionine-supplemented diet on phospholipase C activity in mouse pancreatic acinar cell membranes and in electropermeabilized mouse pancreatic acini

AU - Leli, U.

AU - Saluja, Ashok

AU - Picard, L.

AU - Zavertnik, A.

AU - Steer, M. L.

PY - 1990/1/1

Y1 - 1990/1/1

N2 - The nonhydrolyzable guanyl nucleotide GTPγS stimulated phosphoinositidase C activity in two preparations obtained from mouse pancreatic acini labeled with myo[2-3H]inositol: a cell-free membrane fraction and intact electropermeabilized acini. This action was dose-dependent, was shared by other nonhydrolyzable guanyl nucleotides such as GMP-phencyclidine hydrochloride and GMP-PMP, as well as by fluoride, and was calcium-independent. Contrarily, no effect was observed even at doses of GTPγS as high as 10 μM when the same protocol was repeated on identical acinar preparations from mice fed a choline-deficient, ethionine-supplemented diet. This regiment is known to uncouple secretagogue-receptor occupancy from inositol 1,4,5-trisphosphate generation in pancreatic acinar cells and lead to necrotizing hemorrhagic pancreatitis. These data lead us to conclude that the ethionine-induced inactivation of guanyl nucleotide-dependent pancreatic phosphoinositidase C in pancreatic acinar cells is not the result of either a decrease in GTP level or a decrease in GTP availability. These findings further confirm previous work from this laboratory, which has shown that the biochemical lesion induced by this diet occurs after the agonist-receptor binding step. The diet-induced lesion could be either at the level of the G-protein that couples the enzyme with the receptor or at the level of the phospholipase itself.

AB - The nonhydrolyzable guanyl nucleotide GTPγS stimulated phosphoinositidase C activity in two preparations obtained from mouse pancreatic acini labeled with myo[2-3H]inositol: a cell-free membrane fraction and intact electropermeabilized acini. This action was dose-dependent, was shared by other nonhydrolyzable guanyl nucleotides such as GMP-phencyclidine hydrochloride and GMP-PMP, as well as by fluoride, and was calcium-independent. Contrarily, no effect was observed even at doses of GTPγS as high as 10 μM when the same protocol was repeated on identical acinar preparations from mice fed a choline-deficient, ethionine-supplemented diet. This regiment is known to uncouple secretagogue-receptor occupancy from inositol 1,4,5-trisphosphate generation in pancreatic acinar cells and lead to necrotizing hemorrhagic pancreatitis. These data lead us to conclude that the ethionine-induced inactivation of guanyl nucleotide-dependent pancreatic phosphoinositidase C in pancreatic acinar cells is not the result of either a decrease in GTP level or a decrease in GTP availability. These findings further confirm previous work from this laboratory, which has shown that the biochemical lesion induced by this diet occurs after the agonist-receptor binding step. The diet-induced lesion could be either at the level of the G-protein that couples the enzyme with the receptor or at the level of the phospholipase itself.

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