Endothelins stimulate sodium uptake into rat brain capillary endothelial cells through endothelin A-like receptors.
The effect of endothelins (ETs) on sodium/hydrogen (Na+/H+) antiport system was examined in cultured rat brain capillary endothelium (RBEC). ET-1, ET-2, and ET-3 stimulated Na+ uptake into RBEC with similar half-maximal stimulation (EC50) values (0.7, 0.6, and 1.1 nM, respectively). This reaction was inhibited by the Na+/H+ antiport inhibitor, N-(ethyl-N-isopropyl)-amiloride (EIPA). The selective endothelin A (ETA) receptor-antagonist (cyclo-D-Trp-D-Asp-Pro-D-Val-Leu (BQ123)), but not endothelin B (ETB) receptor-antagonists ((Cys11, Cys15)-ET-1 (IRL1038) or N-cis-2,6-dimethylpiperidinocarbonyl-L-gamma MeLeu-D-Trp(COOMe)-D-Nle-ONa (BQ788)), inhibited both ET-1- and ET-3-stimulated Na+ uptake, indicating ETA-receptor mediation. The protein kinase C (PKC) activator (phorbol 12-myristate 13-acetate (PMA)) failed to stimulate Na+ uptake. The calcium-calmodulin (CaM) inhibitor (W7) reduced ET-1-stimulated Na+ uptake by 50%, whereas the PKC inhibitor (staurosporine) had no effect, indicating that ET-1 stimulation of the Na+/H+ antiport system is linked to a CaM-dependent and PKC-independent pathway.
Kawai
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Stroke Branch, National Institute of Neurological Disorders and Stroke, NIH, Bethesda, MD 20892-4128, USA.
McCarron
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RM
Spatz
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M
D000595:Amino Acid Sequence; D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects*; D002147:Calmodulin / Q000037:antagonists & inhibitors; D002196:Capillaries / Q000187:drug effects / Q000378:metabolism; D065128:Endothelin Receptor Antagonists; D016232:Endothelins / Q000494:pharmacology*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism; D008969:Molecular Sequence Data; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism; D051381:Rats; D017466:Receptors, Endothelin / Q000819:agonists / Q000187:drug effects*; D012964:Sodium / Q000378:metabolism*; D017923:Sodium-Hydrogen Exchangers / Q000378:metabolism; D013268:Stimulation, Chemical; D014662:Vasoconstrictor Agents / Q000494:pharmacology*; D014757:Viper Venoms / Q000494:pharmacology
D002147:Calmodulin; D065128:Endothelin Receptor Antagonists; D016232:Endothelins; D017466:Receptors, Endothelin; D017923:Sodium-Hydrogen Exchangers; D014662:Vasoconstrictor Agents; D014757:Viper Venoms; C057354:sarafotoxins s6; D012964:Sodium; D011493:Protein Kinase C