Acetyl-L-carnitine requires phospholipase C-IP3 pathway activation to induce antinociception

Neuropharmacology
Nicoletta GaleottiCarla Ghelardini

Abstract

The cellular events involved in acetyl-L-carnitine (ALCAR) analgesia were investigated in the mouse hot plate test. I.c.v. pretreatment with aODNs against the alpha subunit of G(q) and G(11) proteins prevented the analgesia induced by ALCAR (100 mg kg(-1) s.c. twice daily for 7 days). Administration of the phospholipase C (PLC) inhibitors U-73122 and neomycin, as well as the injection of an aODN complementary to the sequence of PLCbeta(1), antagonized the increase of the pain threshold induced by ALCAR. Pretreatment with U-73343, an analogue of U-73112 inactive on PLC, did not modify ALCAR analgesic effect. In mice undergoing treatment with LiCl, which impairs phosphatidylinositol synthesis, or pretreatment with TMB-8, a blocker of Ca(++) release from intracellular stores, the antinociception induced by ALCAR was dose-dependently antagonized. I.c.v. treatment with heparin, an IP(3) receptor antagonist, prevented the increase of pain threshold induced by the investigated compound, analgesia that was restored by co-administration of D-myo-inositol. On the other hand, i.c.v. pretreatment with the selective protein kinase C (PKC) inhibitors calphostin C and cheleritryne, resulted in a dose-dependent potentiation of ALCAR antinocice...Continue Reading

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Citations

Aug 19, 2008·Journal of Neuroscience Research·Lorenzo Di Cesare MannelliAlessandro Bartolini
Aug 24, 2007·The European Journal of Neuroscience·Lorenzo Di Cesare MannelliA Bartolini
Jan 13, 2006·Neuroscience Letters·Sarah J L FlattersGary J Bennett
Aug 24, 2013·Expert Review of Neurotherapeutics·Marco OnofrjAstrid Thomas
Sep 26, 2007·CNS Drugs·Santina ChiechioFerdinando Nicoletti
Aug 4, 2021·ACS Chemical Neuroscience·Antonio Espinosa de Los Monteros-ZúñigaAbimael González-Hernández

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