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The effect of a newly developed oral agent, prostaglandin E1 (PGE1) analogue TFC 612, on diabetic neuropathy was studied by giving it for 6 wk to streptozocin-induced diabetic rats that had been diabetic for 3 mo and was compared with the effects of aldose reductase inhibitor ONO 2235. Although both compounds improved decreased motor nerve conduction velocity, the effect of TFC 612 continued during the 6 wk of treatment, whereas that of ONO 2235 became weaker from wk 4. The abnormality in sciatic nerve sorbitol and myo-inositol levels was reversed with ONO 2235, whereas it was unchanged with TFC 612. With the laser Doppler flowmetry technique, a decrease in the sciatic nerve blood flow in diabetic rats was shown to improve with both compounds, but TFC 612 had a greater effect than ONO 2235, and the increased lactate level of the diabetic nerve was corrected with both compounds, suggesting that both may be associated with the amelioration of ischemia in the diabetic endoneurium. Both TFC 612 and ONO 2235 partially but significantly normalized decreased fiber size in diabetic rats. On the other hand, TFC 612 completely normalized the dilated lumen area in diabetic rats, whereas ONO 2235 did not. These results suggest that the PGE1 analogue TFC 612 has a significant effect on diabetic neuropathy, possibly via vasotropic action, and may be a potent compound for the treatment of diabetic neuropathy.

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Three isoforms of catalytic a subunits and two isoforms of /3 subunits of Na + ,K + -ATPase were detected in rat sciatic nerves by western blotting. Unlike the enzyme in brain, sciatic nerve Na,K-ATPase was highly resistant to ouabain. The ouabain-resistant al isoform was demonstrated to be the predominant form in rat intact sciatic nerve by quantitative densitometric analysis and is mainly responsible for sciatic nerve Na~,K~-ATPase activity. After sciatic nerve injury, the a3 and /31 isoforms completely disappeared from the distal segment owing to Wallerian degeneration. In contrast, a2 and /32 isoform expression and Na ,K~-ATPaseactivity sensitive to pyrithiamine (a specific inhibitor of the a2 isoform) were markedly increased in Schwann cells in the distal segment of the injured sciatic nerve. These latter levels returned to baseline with nerve regeneration. Our results suggest that a 3 and /31 isoforms are exclusive for the axon and a2 and /32 isoforms are exclusive for the Schwann cell, although axonal contact regulates a2 and /32 isoform expressions. Because the /32 isoform of Na,K~-ATPaseis known as an adhesion molecule on glia (AMOG), increased expression of AMOG//32 on Schwann cells in the segment distal to sciatic nerve injury suggests that AMOGI/32 may act as an adhesion molecule in peripheral nerve regeneration. Key Words: Na + , K~-ATPase-Sciatic nerve-Regeneration-Adhesion molecule on glia//32-Ouabain. J. Neurochem. 69, 330-339 (1997).Na~,K~-ATPase is a membrane-bound enzyme responsible for active transport of Na and K~and maintaining an electrochemical gradient across the cell membrane. It consists of two subunits, a catalytic a subunit and a glycosylated /3 subunit. The a subunit