GABAergic regulation of enkephalin in rat striatum: alterations in Met5-enkephalin level, precursor content and preproenkephalin messenger RNA abundance.
The influence of chronic activation of gamma-aminobutyric acid (GABA) system on Met5-enkephalin (ME) biosynthesis was investigated in male rats. Activation of GABA system was achieved by raising the brain GABA concentration with aminooxyacetic acid (AOAA) or gabaculine which inhibits GABA-transaminase the enzyme responsible for the catabolism of GABA. After a regimen of repeated administration of AOAA (80 mg/kg/day for 8 days), the GABA concentration in the striatum could be maintained 2-fold greater than control value. AOAA decreased the ME levels in the striatum in a dose (20, 40 and 80 mg/kg)- and time (1-, 2-, 4- and 8-day treatment(s)-dependent fashion. Gabaculine also decreased the ME level in the striatum. Changes in ME level were not observed in other brain regions such as hypothalamus, hippocampus, frontal cortex and medulla/pons. In order to understand the mechanism involved in the decrease in ME level, the biosynthesis of ME was assessed. The preproenkephalin messenger RNA abundance was quantitated by RNA-complementary DNA hybridization technique; the total RNA was isolated, dot-blotted and hybridized with a nick-translated complementary DNA probe from rat brain. Administration of AOAA (80 mg/kg/day) for 8 days increased the preproenkephalin messenger RNA abundance whereas 1-, 2- or 4-day treatments did not alter the levels significantly. A similar trend of response was observed in the cryptic ME level which is indicative of the precursor content. The results suggest that chronic activation of the GABA system induces a sustained release of ME; in order to replenish the depletion, the biosynthesis of ME is augmented.(ABSTRACT TRUNCATED AT 250 WORDS)
D000625:Aminooxyacetic Acid / Q000494:pharmacology; D000818:Animals; D003342:Corpus Striatum / Q000378:metabolism*; D003509:Cyclohexanecarboxylic Acids / Q000494:pharmacology; D004744:Enkephalin, Methionine / Q000378:metabolism; D004745:Enkephalins / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D008297:Male; D011498:Protein Precursors / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D005680:gamma-Aminobutyric Acid / Q000502:physiology*
D003509:Cyclohexanecarboxylic Acids; D004745:Enkephalins; D011498:Protein Precursors; D012333:RNA, Messenger; D000625:Aminooxyacetic Acid; C012987:gabaculine; D005680:gamma-Aminobutyric Acid; D004744:Enkephalin, Methionine; C033660:preproenkephalin