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Congo red modulates ACh-induced Ca(2+) oscillations in single pancreatic acinar cells of mice.

ABSTRACT: AIM: Congo red, a secondary diazo dye, is usually used as an indicator for the presence of amyloid fibrils. Recent studies show that congo red exerts neuroprotective effects in a variety of models of neurodegenerative diseases. However, its pharmacological profile remains unknown. In this study, we investigated the effects of congo red on ACh-induced Ca(2+) oscillations in mouse pancreatic acinar cells in vitro. METHODS: Acutely dissociated pancreatic acinar cells of mice were prepared. A U-tube drug application system was used to deliver drugs into the bath. Intracellular Ca(2+) oscillations were monitored by whole-cell recording of Ca(2+)-activated Cl(-) currents and by using confocal Ca(2+) imaging. For intracellular drug application, the drug was added in pipette solution and diffused into cell after the whole-cell configuration was established. RESULTS: Bath application of ACh (10 nmol/L) induced typical Ca(2+) oscillations in dissociated pancreatic acinar cells. Addition of congo red (1, 10, 100 ?mol/L) dose-dependently enhanced Ach-induced Ca(2+) oscillations, but congo red alone did not induce any detectable response. Furthermore, this enhancement depended on the concentrations of ACh: congo red markedly enhanced the Ca(2+) oscillations induced by ACh (10-30 nmol/L), but did not alter the Ca(2+) oscillations induced by ACh (100-10000 nmol/L). Congo red also enhanced the Ca(2+) oscillations induced by bath application of IP3 (30 ?mol/L). Intracellular application of congo red failed to alter ACh-induced Ca(2+) oscillations. CONCLUSION: Congo red significantly modulates intracellular Ca(2+) signaling in pancreatic acinar cells, and this pharmacological effect should be fully considered when developing congo red as a novel therapeutic drug.

SUBMITTER: Huang ZB

PROVIDER: S-EPMC4261129 | biostudies-literature | 2014 Dec

REPOSITORIES: biostudies-literature

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Congo red modulates ACh-induced Ca(2+) oscillations in single pancreatic acinar cells of mice.

Huang Ze-bing ZB Wang Hai-yan HY Sun Na-na NN Wang Jing-ke JK Zhao Meng-qin MQ Shen Jian-xin JX Gao Ming M Hammer Ronald P RP Fan Xue-gong XG Wu Jie J

Acta pharmacologica Sinica 20141027 12

<h4>Aim</h4>Congo red, a secondary diazo dye, is usually used as an indicator for the presence of amyloid fibrils. Recent studies show that congo red exerts neuroprotective effects in a variety of models of neurodegenerative diseases. However, its pharmacological profile remains unknown. In this study, we investigated the effects of congo red on ACh-induced Ca(2+) oscillations in mouse pancreatic acinar cells in vitro.<h4>Methods</h4>Acutely dissociated pancreatic acinar cells of mice were prepa ...[more]

PMID: 25345744

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Project description:Pancreatic insufficiency (PI) when left untreated results in a state of malnutrition due to an inability to absorb nutrients. Frequently, PI is diagnosed as part of a larger clinical presentation in cystic fibrosis or Shwachman-Diamond syndrome. In this study, a mouse model for isolated exocrine PI was identified in a mouse line generated by a transgene insertion. The trait is inherited in an autosomal recessive pattern, and homozygous animals are growth retarded, have abnormal immunity, and have reduced life span. Mice with the disease locus, named pequeño (pq), exhibit progressive apoptosis of pancreatic acinar cells with severe exocrine acinar cell loss by 8 wk of age, while the islets and ductal tissue persist. The mutation in pq/pq mice results from a random transgene insertion. Molecular characterization of the transgene insertion site by fluorescent in situ hybridization and genomic deletion mapping identified an approximately 210-kb deletion on Chromosome 3, deleting two genes. One of these genes, Serpini2, encodes a protein that is a member of the serpin family of protease inhibitors. Reintroduction of only the Serpini2 gene by bacterial artificial chromosome transgenic complementation corrected the acinar cell defect as well as body weight and immune phenotypes, showing that deletion of Serpini2 causes the pequeño phenotype. Dietary supplementation of pancreatic enzymes also corrected body size, body weight, and immunodeficiency, and increased the life span of Serpini2-deficient mice, despite continued acinar cell loss. To our knowledge, this study describes the first characterized genetic animal model for isolated PI. Genetic complementation of the transgene insertion mutant demonstrates that Serpini2 deficiency directly results in the acinar cell apoptosis, malabsorption, and malnutrition observed in pq/pq mice. The rescue of growth retardation, immunodeficiency, and mortality by either Serpini2 bacterial artificial chromosome transgenic expression or by pancreatic enzyme supplementation demonstrates that these phenotypes are secondary to malnutrition in pq/pq mice.

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Congo red modulates ACh-induced Ca(2+) oscillations in single pancreatic acinar cells of mice.

Publications

Congo red modulates ACh-induced Ca(2+) oscillations in single pancreatic acinar cells of mice.

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