METABOLIC EFFECT OF PGE(1) ANALOG O1206.ALPHA-CD ON NERVE NA-K+-ATPASE ACTIVITY OF RATS WITH STREPTOZOCIN-INDUCED DIABETES IS MEDIATED VIA CAMP - POSSIBLE ROLE OF CAMP IN DIABETIC NEUROPATHY()

We investigated the dose-dependent effects of prostaglandin E(1) (PGE( 1)) analogue, OP1206.alpha CD (OP), on motor nerve conduction velocity (MNCV), nerve blood flow (NBF) and Na+-K+-ATPase (ATPase) activity in streptozocin-induced diabetic rats. At 10 mu g/kg/day, OP ameliorated MNCV and NBF but no ATPase activity, whereas at 30 mu g/kg/day it inc reased MNCV and ATPase activity, but not NBF. These results suggested a possible direct metabolic effect of OP at least at a certain dose, o n ATPase activity independent of NBF. Since PGE(1) exerts an effect on nerve cAMP content, we conducted an in vitro study to clarify the rel ationship of cAMP to the modulation of ATPase activity in diabetic ner ves. We studied sciatic nerves isolated from 53 rats with streptozocin -induced diabetes that had exhibited hyperglycemia for 6 wk. OP increa sed the activity of ATPase and the accumulation of cAMP in a dose-depe ndent manner. Dibutyryl cAMP, a cAMP analogue, and aminophylline, whic h increases nerve cAMP content, enhanced ATPase activity in a dose-dep endent manner. In addition, the increased activity of ATPase in diabet ic nerves produced by OP was suppressed by a protein kinase inhibitor, H8. These results suggest that ATPase activity in diabetic nerves mig ht be regulated or modified by cAMP and, possibly, by protein kinase A , a finding that is important for clarifying the pathogenesis of diabe tic neuropathy and for developing new approaches to treatment.