Cerebral microvascular endothelial cell Na/H exchange: evidence for the presence of NHE1 and NHE2 isoforms and regulation by arginine vasopressin
| العنوان: | Cerebral microvascular endothelial cell Na/H exchange: evidence for the presence of NHE1 and NHE2 isoforms and regulation by arginine vasopressin |
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| المؤلفون: | Martha E O'Donnell, Tina I. Lam, Phyllis M. Wise |
| المصدر: | American Journal of Physiology-Cell Physiology. 297:C278-C289 |
| بيانات النشر: | American Physiological Society, 2009. |
| سنة النشر: | 2009 |
| مصطلحات موضوعية: | Receptors, Vasopressin, Vasopressin, medicine.medical_specialty, Sodium-Hydrogen Exchangers, Arginine, Physiology, Ischemia, Neuropeptide, Blood–brain barrier, Cell Line, chemistry.chemical_compound, Internal medicine, Animals, Protein Isoforms, Medicine, Hypoxia, Receptor, Sodium-Hydrogen Exchanger 1, Estradiol, Cariporide, business.industry, Microcirculation, Brain, Endothelial Cells, Cell Biology, medicine.disease, Rats, Arginine Vasopressin, Endothelial stem cell, Glucose, medicine.anatomical_structure, Endocrinology, nervous system, chemistry, Blood-Brain Barrier, Cerebrovascular Circulation, Cattle, Membrane Transporters, Ion Channels, and Pumps, business |
| الوصف: | Blood-brain barrier (BBB) Na transporters are essential for brain water and electrolyte homeostasis. However, they also contribute to edema formation during the early hours of ischemic stroke by increased transport of Na from blood into brain across an intact BBB. We previously showed that a luminal BBB Na-K-Cl cotransporter is stimulated by hypoxia, aglycemia, and AVP and that inhibition of the cotransporter by intravenous bumetanide significantly reduces edema and infarct in the rat middle cerebral artery occlusion (MCAO) model of stroke. More recently, we found evidence that intravenous cariporide (HOE-642), a highly potent Na/H exchange inhibitor, also reduces brain edema after MCAO. The present study was conducted to investigate which Na/H exchange protein isoforms are present in BBB endothelial cells and to evaluate the effects of ischemic factors on BBB Na/H exchange activity. Western blot analysis of bovine cerebral microvascular endothelial cells (CMEC) and immunoelectron microscopy of perfusion-fixed rat brain revealed that Na/H exchanger isoforms 1 and 2 (NHE1 and NHE2) are present in BBB endothelial cells. Using microspectrofluorometry and the pH-sensitive dye BCECF, we found that hypoxia (2% O2, 30 min), aglycemia (30 min), and AVP (1–200 nM, 5 min) significantly increased CMEC Na/H exchange activity, assessed as Na-dependent, HOE-642-sensitive H+flux. We found that AVP stimulation of CMEC Na/H exchange activity is dependent on intracellular Ca concentration and is blocked by V1, but not V2, vasopressin receptor antagonists. Our findings support the hypothesis that a BBB Na/H exchanger, possibly NHE1 and/or NHE2, is stimulated during ischemia to participate in cerebral edema formation. |
| تدمد: | 1522-1563 0363-6143 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::9ab30c0330891893e1cd462d18b3c4b0Test https://doi.org/10.1152/ajpcell.00093.2009Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....9ab30c0330891893e1cd462d18b3c4b0 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15221563 03636143 |
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