A pentylenetetrazole-induced generalized seizure in early life enhances the efficacy of muscarinic receptor coupling to G-protein in hippocampus and neocortex of adult rat.
We have previously shown that exposure to the anti-cholinesterase eserine provokes interictal-like discharges in the CA3 area of hippocampal slices from adult rats in which a generalized seizure has been induced by pentylenetetrazole (PTZ) when immature (at 20 days). Such increased responsiveness to acetylcholine (ACh) was not associated with any change in hippocampal acetylcholine or gamma-aminobutyric acid (GABA) content, GABAergic inhibition or density of ACh innervation, but was blocked by the muscarinic receptor antagonist atropine. We therefore turned to quantitative radioligand binding autoradiography, in situ hybridization and the [35S]GTPgammaS method to assess the properties of hippocampal and neocortical muscarinic receptors in adult rats having experienced a PTZ seizure at P20. The densities of M1 and M2 receptor binding sites, respectively labeled with [3H]pirenzepine and [3H]AFDX-384, as well as the amount of m1, m2 and m3 receptor mRNAs, did not differ from control in the hippocampus and neocortex of these rats. In contrast, in PTZ rats, both brain regions displayed a marked increase in [35S]GTPgammaS incorporation stimulated by ACh, bethanechol and particularly oxotremorine. This finding indicates that a generalized seizure in immature rat can entail a long-term and presumably permanent increase in the efficacy of G-protein coupling to muscarinic receptors in the hippocampus and neocortex of the adult. By analogy, such a mechanism could account for the susceptibility to epilepsy of human adults having suffered from prolonged convulsions in early life.
Potier
Soizic
S
Ste-Justine Hospital Research Centre & Department of Pediatrics, Montreal, Québec, Canada.
Sénécal
Jacques
J
Chabot
Jean-Guy
JG
Psarropoulou
Caterina
C
Descarries
Laurent
L
D000818:Animals; D001345:Autoradiography / Q000379:methods; D004347:Drug Interactions; D005260:Female; D019204:GTP-Binding Proteins / Q000378:metabolism*; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D017403:In Situ Hybridization / Q000379:methods; D008297:Male; D018721:Muscarinic Agonists / Q000494:pharmacology; D019579:Neocortex / Q000187:drug effects / Q000378:metabolism*; D010276:Parasympatholytics / Q000494:pharmacology; D010433:Pentylenetetrazole / Q000494:pharmacology; D010890:Pirenzepine / Q000031:analogs & derivatives* / Q000494:pharmacology; D051381:Rats; D011976:Receptors, Muscarinic / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D012640:Seizures / Q000139:chemically induced / Q000378:metabolism*; D012737:Sex Factors; D013449:Sulfonamides / Q000494:pharmacology; D013460:Sulfur Isotopes / Q000494:pharmacology; D014316:Tritium / Q000494:pharmacology
D018721:Muscarinic Agonists; D010276:Parasympatholytics; D011976:Receptors, Muscarinic; D013449:Sulfonamides; D013460:Sulfur Isotopes; D014316:Tritium; C065959:AFDX 384; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D010890:Pirenzepine; C015451:piretanide; D019204:GTP-Binding Proteins; D010433:Pentylenetetrazole