Carnitine inhibits hydrolysis of inositol phospholipids induced by activation of metabotropic receptors.
We previously found that carnitine prevents glutamate neurotoxicity and that this effect is mediated by activation of metabotropic glutamate receptors. We show now that carnitine inhibits the hydrolysis of inositol phospholipids induced by different agonists of metabotropic glutamate receptors (tACPD; (+/-)-1-aminocyclopentane-trans-1,3-dicarboxylic acid; DHPG, (R,S)-3,5-dyhydroxyphenylglycine or S4C3HPG, (S)-4-carboxy-3-hydroxyphenylglycine). The EC50 was ca. 170 microM and the inhibition was complete at 1 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 phospholipase C activity but inhibits partially (43%) the hydrolysis of inositol phospholipids induced by direct activation of G proteins with AIF4-. The results reported indicate that carnitine inhibits the hydrolysis of inositol phospholipids induced by activation of metabotropic receptors likely by interfering the function of some types of G proteins.
Llansola
M
M
Instituto de Investigaciones Citológicas de la Fundación Valenciana de Investigaciones Biomédicas, Valencia, Spain.
Felipo
V
V
D000818:Animals; D002217:Carbachol / Q000494:pharmacology; D002331:Carnitine / Q000494:pharmacology*; D002396:Catechols / Q000494:pharmacology; D003515:Cycloleucine / Q000031:analogs & derivatives / Q000494:pharmacology; D019204:GTP-Binding Proteins / Q000378:metabolism; D005998:Glycine / Q000031:analogs & derivatives / Q000494:pharmacology; D006624:Hippocampus / Q000378:metabolism; D006868:Hydrolysis; D008297:Male; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009638:Norepinephrine / Q000494:pharmacology; D010716:Phosphatidylinositols / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D018094:Receptors, Metabotropic Glutamate / Q000819:agonists / Q000502:physiology*; D010738:Type C Phospholipases / Q000187:drug effects / Q000378:metabolism
D002396:Catechols; D018696:Neuroprotective Agents; D010716:Phosphatidylinositols; D018094:Receptors, Metabotropic Glutamate; D003515:Cycloleucine; C036361:1-amino-1,3-dicarboxycyclopentane; C078245:4-carboxy-3-hydroxyphenylglycine; C099561:3,4-dihydroxyphenylglycine; D002217:Carbachol; D010738:Type C Phospholipases; D019204:GTP-Binding Proteins; D002331:Carnitine; D005998:Glycine; D009638:Norepinephrine