Autoanti-phosphatidylinositide antibodies specifically inhibit noradrenaline effects on Ca2+ and Cl- channels in rat portal vein myocytes

High levels of circulating autoantibodies (auto-Ab) directed against phosphatidylinositides have been identified in the sera of patients with malignant tumors. These polyclonal autoantibodies had higher avidity and specificity for phosphatidylinositol (PtdIns) than for the other phosphatidylinositid...

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Bibliographic Details
Published in:The Journal of biological chemistry 1992-03, Vol.267 (7), p.4312-4316
Main Authors: LOIRAND, G, FAIDERBE, S, BARON, A, GEFFARD, M, MIRONNEAU, J
Format: Article
Language:English
Subjects:
Acetylcholine - pharmacology
Animals
Autoantibodies - immunology
Biochemistry & Molecular Biology
Biological and medical sciences
Biophysics
Caffeine - pharmacology
Calcium Channels - metabolism
Calcium Channels - physiology
Cardiology and cardiovascular system
Cell Behavior
Cell physiology
Cellular Biology
Chloride Channels
Diglycerides - metabolism
Enzyme-Linked Immunosorbent Assay
Fundamental and applied biological sciences. Psychology
Human health and pathology
Humans
Inositol 1,4,5-Trisphosphate - metabolism
Life Sciences
Life Sciences & Biomedicine
Membrane Potentials - drug effects
Membrane Proteins - metabolism
Membrane Proteins - physiology
Molecular and cellular biology
Muscle, Smooth, Vascular - cytology
Muscle, Smooth, Vascular - metabolism
Muscle, Smooth, Vascular - physiology
Norepinephrine - antagonists & inhibitors
Phosphatidylinositols - immunology
Portal Vein - cytology
Portal Vein - metabolism
Protein Kinase C - metabolism
Rats
Receptors, Adrenergic, alpha - metabolism
Science & Technology
Signal Transduction
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Summary:High levels of circulating autoantibodies (auto-Ab) directed against phosphatidylinositides have been identified in the sera of patients with malignant tumors. These polyclonal autoantibodies had higher avidity and specificity for phosphatidylinositol (PtdIns) than for the other phosphatidylinositides. Effects of the auto-Ab were studied in smooth muscle myocytes in the PtdIns-involving transduction mechanism triggered by activation of alpha 1-adrenoceptors. Noradrenaline activated a Ca(2+)-dependent Cl- current through the Ca(2+)-releasing action of inositol 1,4,5-trisphosphate (InsP3) and enhanced the Ca2+ channel current through a diacylglycerol and protein kinase C-dependent mechanism. External applications of auto-Ab (0.03-0.3 mg/ml) were without effect on noradrenaline-induced responses whereas intracellular applications (0.0004-0.012 mg/ml) inhibited both Cl- current activation and Ca2+ channel current stimulation. Intracellular applications of IgG from healthy donors had no effect on noradrenaline-induced responses. When anti-PtdIns Ab were preincubated with PtdIns the inhibition of the noradrenaline-induced responses on Ca2+ and Cl- channels was not observed. Autoanti-PtdIns Ab inhibited also the acetylcholine-activated Cl- current, confirming that the acetylcholine response was mediated through the phosphatidylinositol breakdown. In contrast, the autoanti-PtdIns Ab were ineffective against the transduction pathway after beta-adrenoceptor activation. Therefore, these results suggest that the biological effect of autoanti-PtdIns Ab results from a specific binding to membrane PtdIns or PtdIns metabolites and thereby prevented InsP3 and diacylglycerol production. These autoanti-PtdIns Ab appear to be a new specific tool to identify the role of phosphatidylinositides in intracellular transduction processes.
ISSN:0021-9258
1083-351X
DOI:10.1016/S0021-9258(18)42835-9