Long-lasting Enhancement of Metabotropic Excitatory Amino Acid Receptor-mediated Polyphosphoinositide Hydrolysis in the Amygdala/pyriform Cortex of Deep Prepiriform Cortical Kindled Rats
Affiliations
We have previously demonstrated that ibotenate (IBO)-stimulated polyphosphoinositide (PPI) hydrolysis is increased for a long period in the amygdala/pyriform cortex (AM/PC) of amygdala (AM)- and hippocampal (HIPP)-kindled rats. This finding indicates that enhanced function of the PPI-coupled excitatory amino acid (EAA) receptor may be associated with the long-lasting seizure susceptibility of kindling. The present study further examined PPI hydrolysis induced by trans-ACPD, a selective agonist of the metabotropic EAA receptor, as well as by IBO in brain slices of rats kindled from the deep prepiriform cortex (DPC). IBO-stimulated accumulation of [3H]inositol monophosphate ([3H]InsP) was significantly increased in the AM/PC by 162 (P less than 0.0001), 130 (P less than 0.005) and 81% (P less than 0.03) at 24 h, 7 days and 28 days, respectively, after the last kindled seizure, whereas it was increased significantly only at 24 h after the last seizure in the HIPP and did not change at any time in the limbic forebrain (LFB). The IBO-stimulated accumulation of [3H]InsP was significantly increased by 55% (P less than 0.01) in the AM/PC of partially kindled rats reaching an average stage of 3.7, but not in the AM/PC of those remaining at stage 1, 7 days after the last kindled seizure. Trans-ACPD-stimulated PPI hydrolysis was significantly increased in the AM/PC of DPC-kindled rats by 65 (P less than 0.05) and 45% (P less than 0.005) at 7 and 28 days, respectively, after the last kindled seizure. Cis-ACPD-stimulated PPI hydrolysis was also significantly increased in the AM/PC of DPC-kindled rats by 45 (P less than 0.03) and 30% (P less than 0.04) at 7 and 28 days, respectively, after the last seizure. There was no increase in trans-ACPD- or cis-ACPD-stimulated PPI hydrolysis in the HIPP or LFB. These results further confirm our previous studies showing that the metabotropic EAA receptor-stimulated PPI hydrolysis exhibited a long-lasting increase in the AM/PC irrespective of the primary stimulation site for kindling.
Kanchi S, Meesala G J Epilepsy Res. 2024; 14(1):21-28.
PMID: 38978532 PMC: 11227920. DOI: 10.14581/jer.24004.
Molecular targets for antiepileptic drug development.
Meldrum B, Rogawski M Neurotherapeutics. 2007; 4(1):18-61.
PMID: 17199015 PMC: 1852436. DOI: 10.1016/j.nurt.2006.11.010.
Keele N, Arvanov V J Physiol. 1997; 499 ( Pt 1):87-104.
PMID: 9061642 PMC: 1159339. DOI: 10.1113/jphysiol.1997.sp021913.
Delahunty T, Jiang J, Black R, Lyeth B Neurochem Res. 1995; 20(4):405-11.
PMID: 7651577 DOI: 10.1007/BF00973095.