| [ Summary ] |
The increased synthesis of guanidinosuccinate (GSA) and methylguanidine (MG) known as uremic toxin has been noted. Recently, vasodilation with the increase of cGMP and activation of NMDA receptor by GSA and the inhibition of iNOS by MG were reported as new actions of these compounds.
We clarified the following. 1) GSA is formed from reactive oxygen and argininosuccinate which might be increased by the addition of urea. 2) MG is formed via an intermediate (identified as creatol) Iater, that is, it is formed from a hydroxyl radical and creatinine. 3) Puromycin aminonucleoside (PAN) increased MG synthesis. 4) This increase of MG synthesis is inhibited by a protein kinase C (PKC)inhibitor. 5) PAN rapidly activated PKC in rat kidney tissue. These results suggested that hydroxyl radical generation in tissue cells may be increased by PKC activation. PKC activation is expected in those patients with severe hyperparathyroidism whose MG synthesis has increased. |