Culliford S J, Ellory J C, Gibson J S, Speake P F
University Laboratory of Physiology, Parks Road, Oxford, OX1 3PT, UK.
Pflugers Arch. 1998 Apr;435(5):740-2. doi: 10.1007/s004240050576.
K influx and efflux (both ouabain- and bumetanide-resistant) in haemoglobin S-containing red cells (sickle cells) were markedly stimulated by urea (> 0.25 M). Stimulation was rapid and reversible. Volume-sensitive KCl cotransport in both HbA or HbS red cells is thought to be O2-dependent but we show here that urea-stimulated K fluxes in sickle cells were largely insensitive to O2 tension. Urea-stimulated K fluxes were not inhibited by lowering the external Ca concentration (with EGTA) but were abolished by Cl-substitution (with MeSO4 or NO3) or pretreatment of cells with the protein phosphatase inhibitor, calyculin A (0.1 muM). Results are consistent with a stimulatory action of urea on the KCl cotransporter, independent of oxygen tension, mediated via the phosphorylation cascade which regulates the transporter. The importance of this effect to the physiology and pathology of sickle cells is discussed.
含血红蛋白S的红细胞（镰状细胞）中的钾离子流入和流出（均对哇巴因和布美他尼耐药）受到尿素（>0.25M）的显著刺激。刺激迅速且可逆。人们认为HbA或HbS红细胞中的容量敏感性氯化钾协同转运依赖于氧气，但我们在此表明，镰状细胞中尿素刺激的钾离子通量在很大程度上对氧张力不敏感。降低细胞外钙浓度（用乙二醇双四乙酸）不会抑制尿素刺激的钾离子通量，但用氯离子替代物（用甲磺酸盐或硝酸盐）或用蛋白磷酸酶抑制剂花萼海绵诱癌素A（0.1μM）预处理细胞会消除这种通量。结果表明，尿素对氯化钾协同转运体具有刺激作用，该作用不依赖于氧张力，是通过调节转运体的磷酸化级联反应介导的。本文讨论了这种效应对镰状细胞生理和病理的重要性。
