GABAergic regulation of enkephalin in rat striatum: Alterations in Met5-enkephalin level, precursor content and preproenkephalin messenger RNA abundance

S. P. Sivam, J. S. Hong

Research output: Contribution to journalArticle

27 Scopus citations

Abstract

The influence of chronic activation of γ-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 treatments)-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 biopsynthesis of ME is augmented. In view of the colocalization of GABA and ME in the striatal neurons and the known inhibitory function of these substances in neurotransmission process, the evidence presented here suggests a complex functional interaction between GABA and opioid peptide transmitter systems.

Original languageEnglish (US)
Pages (from-to)326-331
Number of pages6
JournalJournal of Pharmacology and Experimental Therapeutics
Volume237
Issue number1
StatePublished - Jan 1 1986
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology

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