Extracellular calcium is required for the polychlorinated biphenyl-induced increase of intracellular free calcium levels in cerebellar granule cell culture
| Autor: | Timothy J. Shafer, Prasada Rao S. Kodavanti, Hugh A. Tilson, William R. Mundy |
|---|---|
| Rok vydání: | 1999 |
| Předmět: |
Thapsigargin
Receptors Cytoplasmic and Nuclear chemistry.chemical_element Mitochondria Liver Muscarinic Agonists Calcium Biology Toxicology Muscarinic agonist Structure-Activity Relationship chemistry.chemical_compound Cerebellum Extracellular Animals Inositol 1 4 5-Trisphosphate Receptors Rats Long-Evans Inositol Cells Cultured Neurons Calcium metabolism Dose-Response Relationship Drug L-Lactate Dehydrogenase Polychlorinated Biphenyls Rats Animals Newborn chemistry Biochemistry Microsomes Liver Microsome Carbachol Environmental Pollutants Calcium Channels Intracellular |
| Zdroj: | Toxicology. 136:27-39 |
| ISSN: | 0300-483X |
| Popis: | Recent studies from the laboratory indicate that polychlorinated biphenyl (PCB) congeners can alter signal transduction and calcium homeostasis in neuronal preparations. These effects were more pronounced for the ortho -substituted, non-coplanar congeners, although the mechanisms underlying these effects are not clear. In the present study the time-course and concentration-dependent effects of coplanar and non-coplanar PCBs on intracellular free calcium concentration ([Ca 2+ ] i ) in cerebellar granule cell cultures were compared using the fluorescent probe fura-2. The ortho -substituted congeners 2,2′-dichlorobiphenyl (DCB) and 2,2′,4,6,6′-pentachlorobiphenyl (PeCB) caused a gradual increase of [Ca 2+ ] i while the non- ortho -substituted congeners 4,4′-DCB and 3,3′,4,4′,5-PeCB had no effect. The increase of [Ca 2+ ] i produced by 2,2′-DCB was time- and concentration-dependent. Further studies examined possible mechanisms for this rise in [Ca 2+ ] i . In contrast to the muscarinic agonist carbachol, the effects of 2,2′-DCB on [Ca 2+ ] i were not blocked by thapsigargin and required the presence of extracellular calcium. The effects of ortho -substituted PCBs may depend on their ability to inhibit calcium sequestration as 2,2′-DCB significantly inhibited 45 Ca 2+ -uptake by microsomes and mitochondria while 3,3′,4,4′,5-PeCB had no effect. In addition, 2,2′-DCB significantly increased the binding of [ 3 H]inositol 1,4,5-trisphosphate to receptors on cerebellar microsomes, suggesting another possible mechanism by which ortho -substituted PCBs can mobilize [Ca 2+ ] i . These results show that PCBs increase [Ca 2+ ] i in vitro via a mechanism that requires extracelluar calcium, and support previous structure-activity studies indicating that ortho -substituted PCBs are more potent than non- ortho -substituted PCBs. |
| Databáze: | OpenAIRE |
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