Quinolinic acid elevates striatal and pallidal Met-enkephalin levels: the role of enkephalin synthesis and release.
Huntington's chorea (HC) is characterized, in part, by a substantial deficit in the striatal and pallidal enkephalin levels. Recently, an attempt was made to replicate this deficit by focally injecting quinolinic acid (QUIN), an excitotoxin, into the rat striatum. However, at 7 days post-injection, QUIN produced a dose-related and bilateral increase in the striatal and pallidal levels of met-enkephalin-like immunoreactivity (ME-i.r.), an effect which was attenuated in the presence of excitatory amino acid (EAA) receptor antagonists. In the present study, the action of QUIN was investigated further. To determine whether the QUIN (72 nmol)-induced elevations in ME-i.r. reflected the enhanced synthesis of the peptide, the striatal levels of proenkephalin mRNA were assayed 7 days following a unilateral injection of QUIN into the rat striatum. QUIN significantly depleted (50%) of the proenkephalin mRNA level in the injected, but not the contralateral striatum when compared to that in the saline-injected animals. To determine whether the QUIN-induced increases in ME-i.r. were due to an impaired release of the peptide, the release of ME-i.r. from the striatal or pallidal slices obtained from animals 7 days after a saline- or QUIN-injection, was measured. The 30 mM K(+)-stimulated ME-i.r. release from the saline-injected and contralateral striatum represented an 8-fold increase above the spontaneous release level, while this stimulus induced a 6-fold increase in the ME-i.r. release from both the QUIN-injected and contralateral striatum.(ABSTRACT TRUNCATED AT 250 WORDS)
Ruzicka
B B
BB
Department of Pharmacology and Toxicology, Queen's University, Kingston, Ont., Canada.
Day
R
R
Jhamandas
K
K
D000818:Animals; D015152:Blotting, Northern; D003342:Corpus Striatum / Q000187:drug effects / Q000502:physiology*; D004744:Enkephalin, Methionine / Q000096:biosynthesis / Q000378:metabolism*; D004745:Enkephalins / Q000235:genetics*; D005071:Evoked Potentials / Q000187:drug effects; D005917:Globus Pallidus / Q000187:drug effects / Q000502:physiology*; D008297:Male; D011498:Protein Precursors / Q000235:genetics*; D017378:Quinolinic Acid; D011805:Quinolinic Acids / Q000008:administration & dosage / Q000494:pharmacology*; D015347:RNA Probes; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011863:Radioimmunoassay; D051381:Rats; D011919:Rats, Inbred Strains; D013238:Stereotaxic Techniques
D004745:Enkephalins; D011498:Protein Precursors; D011805:Quinolinic Acids; D015347:RNA Probes; D012333:RNA, Messenger; C029992:proenkephalin; D004744:Enkephalin, Methionine; D017378:Quinolinic Acid