CARNITINE INHIBITS HYDROLYSIS OF INOSITOL PHOSPHOLIPIDS INDUCED BY ACTIVATION OF METABOTROPIC RECEPTORS

We previously found that carnitine prevents glutamate neurotoxicity an d that this effect is mediated by activation of metabotropic glutamate receptors. We show now that carnitine inhibits the hydrolysis of inos itol phospholipids induced by different agonists of metabotropic gluta mate receptors (tACPD; (+/-)-1-aminocyclopentane-trans-1,3-dicarboxyli c acid; DHPG, (R,S)-3,5-dyhydroxyphenylglycine or S4C3HPG, (S)-4-carbo xy-3-hydroxyphenylglycine). The EC50 was ca. 170 mu M and the inhibiti on was complete at I mM carnitine. Carnitine also inhibits completely hydrolysis of inositol phospholipids induced by arterenol (agonist of adrenoceptors) and only partially (ca. 50%) that induced by carbachol (agonist of muscarinic receptors). Carnitine did not inhibit phospholi pase C activity but inhibits partially (43%) the hydrolysis of inosito l phospholipids induced by direct activation of G proteins with AlF4-. The results reported indicate that carnitine inhibits the hydrolysis of inositol phospholipid induced by activation of metabotropic recepto rs likely by interfering the function of some types of G proteins.