Ze-bing Huang1, Hai-yan Wang2, Na-na Sun2, Jing-ke Wang2, Meng-qin Zhao2, Jian-xin Shen2, Ming Gao3, Ronald P Hammer4, Xue-gong Fan5, Jie Wu6. 1. 1] Department of Infectious Diseases, Xiangya Hospital, Central South University, and Key Laboratory of Viral Hepatitis, Changsha 410008, China [2] Divisions of Neurology and Neurobiology, Barrow Neurological Institute, St Joseph's Hospital and Medical Center, Phoenix, AZ 8501, USA [3] Departments of Basic Medical Sciences, Pharmacology and Psychiatry, University of Arizona College of Medicine, Phoenix, AZ 85004, USA. 2. Department of Physiology, Shantou University of Medical College, Shantou 210854, China. 3. Divisions of Neurology and Neurobiology, Barrow Neurological Institute, St Joseph's Hospital and Medical Center, Phoenix, AZ 8501, USA. 4. Departments of Basic Medical Sciences, Pharmacology and Psychiatry, University of Arizona College of Medicine, Phoenix, AZ 85004, USA. 5. Department of Infectious Diseases, Xiangya Hospital, Central South University, and Key Laboratory of Viral Hepatitis, Changsha 410008, China. 6. 1] Department of Infectious Diseases, Xiangya Hospital, Central South University, and Key Laboratory of Viral Hepatitis, Changsha 410008, China [2] Divisions of Neurology and Neurobiology, Barrow Neurological Institute, St Joseph's Hospital and Medical Center, Phoenix, AZ 8501, USA [3] Department of Physiology, Shantou University of Medical College, Shantou 210854, China [4] Departments of Basic Medical Sciences, Pharmacology and Psychiatry, University of Arizona College of Medicine, Phoenix, AZ 85004, USA.
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 μmol/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 μmol/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.
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 mousepancreatic 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 μmol/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 μmol/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.
Authors: Ciara M Walsh; Michael Chvanov; Lee P Haynes; Ole H Petersen; Alexei V Tepikin; Robert D Burgoyne Journal: Biochem J Date: 2009-12-14 Impact factor: 3.857
Authors: Christofer Lendel; Benedetta Bolognesi; Anna Wahlström; Christopher M Dobson; Astrid Gräslund Journal: Biochemistry Date: 2010-02-23 Impact factor: 3.162