Effects of Triphenyltin on Cytosolic Na+ and Ca2+ Response to Glucose and Acetylcholine in Pancreatic β-Cells from Hamster
| Autor: | Yoshikazu Miura, Hisao Matsui |
|---|---|
| Rok vydání: | 2001 |
| Předmět: |
Male
medicine.medical_specialty Triphenyltin chloride Fura-2 Sodium Hamster chemistry.chemical_element Calcium Toxicology Ouabain Islets of Langerhans chemistry.chemical_compound Cytosol Cricetinae Internal medicine Insulin Secretion Organotin Compounds medicine Extracellular Animals Insulin Enzyme Inhibitors Pharmacology Mesocricetus Acetylcholine Glucose Endocrinology chemistry Sodium-Potassium-Exchanging ATPase medicine.drug |
| Zdroj: | Toxicology and Applied Pharmacology. 174:1-9 |
| ISSN: | 0041-008X |
| Popis: | Oral administration of triphenyltin chloride (TPT) (60 mg/kg body wt) inhibits insulin secretion by perturbing the cytoplasmic Ca(2+) concentration ([Ca(2+)]i) in pancreatic beta-cells of the hamster. To test the possibility that the abnormal levels of [Ca(2+)]i induced by TPT administration could be due to a defect in the cytoplasmic Na(+) concentration ([Na(+)]i) in the beta-cells, we investigated the effects of TPT administration on the changes of [Na(+)]i and [Ca(2+)]i induced by glucose or acetylcholine (ACh) and on the [Na(+)]i induced by ouabain, a potent inhibitor of Na(+),K(+)-ATPase. The changes of [Na(+)]i and [Ca(2+)]i were measured in islet cells loaded with sodium-binding benzofuran isophthalate and fura 2, respectively. TPT administration strongly reduced the rise in [Ca(2+)]i induced by 15 mM glucose with and without extracellular 135 mM Na(+). TPT administration also significantly reduced the rise of [Ca(2+)]i by 100 microM ACh in the presence of 5.5 or 15 mM glucose but not the amplitude of [Ca(2+)]i by 100 microM ACh in Na(+)-free medium. TPT administration attenuated the rise in [Na(+)]i induced by 100 microM ACh in the presence of either 3 or 5.5 mM glucose. However, TPT administration did not impair the [Na(+)]i in the presence of glucose (3, 5.5, and 15 mM) or of 100 microM ouabain with 3 mM glucose. TPT administration significantly suppressed the insulin secretion induced by 15 and 27.8 mM glucose or 100 microM ACh in the presence of 5.5 mM glucose. Our study suggests that triphenyltin has inhibitory effects on the cellular Ca(2+) response due to a reduction of [Ca(2+)]i after Na(+)-dependent and Na(+)-independent depolarization in islet cells of the hamster. |
| Databáze: | OpenAIRE |
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