Ca2+ uptake, fatty acid, and LDH release during proximal tubule hypoxia: effects of mepacrine and dibucaine
| Autor: | Raphael A. Nemenoff, Robert W. Schrier, Patricia E. Gengaro, D. Bunnachak, Thomas J. Burke, A. R. P. Almeida, Jack F.M. Wetzels |
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| Rok vydání: | 1994 |
| Předmět: |
medicine.medical_specialty
Time Factors Physiology Mepacrine Dibucaine chemistry.chemical_element Fatty Acids Nonesterified In Vitro Techniques Calcium Phospholipase Kidney Tubules Proximal chemistry.chemical_compound Internal medicine Lactate dehydrogenase medicine Animals Hypoxia Calcium metabolism Dose-Response Relationship Drug L-Lactate Dehydrogenase Chemistry Biological Transport Hypoxia (medical) Rats Kinetics Dose–response relationship Endocrinology Quinacrine medicine.symptom medicine.drug |
| Zdroj: | American Journal of Physiology-Renal Physiology. 266:F196-F201 |
| ISSN: | 1522-1466 1931-857X |
| Popis: | In freshly isolated hypoxic rat proximal tubules, Ca2+ uptake rate increases promptly, within 1 min, and remains significantly elevated throughout a 20-min period of hypoxia. Lactate dehydrogenase (LDH) release, a sign of membrane injury, increases only after 5 min of hypoxia and thereafter rises progressively. The potential effect of increased Ca2+ uptake rate to activate phospholipases, which would then initiate membrane injury, was evaluated by treating hypoxic tubules with three dissimilar phospholipase inhibitors, i.e., mepacrine, dibucaine, or p-bromophenacyl bromide (PBPB). LDH release averaged 11.9 and 13.8% after 10 and 20 min of normoxia, respectively. With 10 or 20 min of hypoxia LDH release increased to 46.0 and 65.2%, respectively (P < 0.01), and Ca2+ uptake rate increased from 2.56 in normoxia to 4.71 nmol.mg-1 x min-1 at 10 min of hypoxia (P < 0.01) and from 2.82 in normoxia to 3.76 nmol/mg at 20 min of hypoxia (P < 0.05). In a separate series of tubules, after 10 min of hypoxia LDH release was reduced by pretreatment with 50 microM mepacrine (66.1 to 47.3%, P < 0.01) or 50 microM dibucaine (53.1 to 38.5%, P < 0.02). The increase in Ca2+ uptake rate also was significantly reduced. After 20 min of hypoxia neither mepacrine nor dibucaine reduced Ca2+ uptake rate; LDH release was modestly reduced by dibucaine but not mepacrine. Higher doses of mepacrine (500 microM) and dibucaine (250 microM) also reduced cell injury at 10 min of hypoxia as assessed by LDH release.(ABSTRACT TRUNCATED AT 250 WORDS) |
| Databáze: | OpenAIRE |
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