Simmons D A, Winegrad A I
Cox Institute, Department of Medicine, School of Medicine, University of Pennsylvania, Philadelphia.
Diabetologia. 1991 Mar;34(3):157-63. doi: 10.1007/BF00418269.
The mechanism by which hyperglycaemia causes decreased (Na+,K+)-ATPase activity preventable by aldose reductase inhibitors and by raising plasma myo-inositol in specific tissues can be activated in vitro in normal rabbit aortic wall; it selectively inhibits a component of resting (Na+,K+)-ATPase activity maintained by a novel regulatory system through rapid basal phosphatidylinositol turnover (hydrolysis) in a discrete pool, which is replenished by a fraction of phosphatidylinositol synthesis that selectively requires myo-inositol transport. A role for endogenously released adenosine in this regulatory system was examined. Adding adenosine deaminase or 8-phenyltheophylline, an adenosine receptor antagonist, selectively inhibited the component of (Na+,K+)-ATPase activity maintained by the regulatory system; when inhibited with adenosine deaminase this component was restored by 2-chloroadenosine, 5'-N-ethylcarbox-amidoadenosine, and 1-oleoyl-2-acetylglycerol, but not by forskolin (which also did not inhibit this component). Adenosine deaminase inhibited the rapid basal turnover of the discrete phosphatidylinositol pool, and 2-chloroadenosine then stimulated its turnover. Raising medium glucose from 5 to 10-30 mmol/l inhibits the regulatory system by making myo-inositol transport at a normal plasma level inadequate to maintain the replenishment of the discrete phosphatidylinositol pool. 2-Chloroadenosine stimulation of the "adenosine-sensitive" component of (Na+,K+)-ATPase activity was inhibited in tissue incubated with 30 mmol/l glucose and myo-inositol in a normal plasma level, but this effect was demonstrable when the medium myo-inositol was raised seven-fold. Hyperglycaemia-induced decreased (Na+,K+)-ATPase activity that is preventable by aldose reductase inhibitors and by raising plasma myo-inositol results from the inhibition of a novel adenosine-(Na+,K+)-ATPase regulatory system.
高血糖导致（Na⁺，K⁺）-ATP酶活性降低的机制可被醛糖还原酶抑制剂以及通过提高特定组织中的血浆肌醇所预防，该机制在体外正常兔主动脉壁中可被激活；它选择性抑制由一种新型调节系统维持的静息（Na⁺，K⁺）-ATP酶活性的一个组分，该调节系统通过离散池中快速的基础磷脂酰肌醇周转（水解）来实现，而该离散池由一部分选择性需要肌醇转运的磷脂酰肌醇合成来补充。研究了内源性释放的腺苷在该调节系统中的作用。添加腺苷脱氨酶或腺苷受体拮抗剂8-苯基茶碱可选择性抑制由该调节系统维持的（Na⁺，K⁺）-ATP酶活性组分；当用腺苷脱氨酶抑制时，该组分可被2-氯腺苷、5'-N-乙基羧基酰胺腺苷和1-油酰-2-乙酰甘油恢复，但不能被福斯可林恢复（福斯可林也不抑制该组分）。腺苷脱氨酶抑制离散磷脂酰肌醇池的快速基础周转，然后2-氯腺苷刺激其周转。将培养基葡萄糖从5 mmol/l提高到10 - 30 mmol/l会抑制该调节系统，因为在正常血浆水平下肌醇转运不足以维持离散磷脂酰肌醇池的补充。在含有30 mmol/l葡萄糖且肌醇处于正常血浆水平的组织中，2-氯腺苷对（Na⁺，K⁺）-ATP酶活性“腺苷敏感”组分的刺激作用受到抑制，但当培养基中的肌醇提高7倍时，这种作用就会显现出来。醛糖还原酶抑制剂和提高血浆肌醇可预防的高血糖诱导的（Na⁺，K⁺）-ATP酶活性降低是由一种新型腺苷-（Na⁺，K⁺）-ATP酶调节系统的抑制所致。
