Changes in the metabolism and binding of GABA in the rat brain in thioacetamide-induced hepatogenic encephalopathy.
The GABA level, and the glutamic acid decarboxylase (GAD) and GABA-aminotransferase (GABA-T) activities were measured in the cortex and striatum of rats in which the early stages of hepatogenic encephalopathy (HE) had been induced by few intraperitoneal administrations of thioacetamide (TAA). Besides, the GABA binding to synaptic plasma membranes (SPM) isolated from whole brain hemispheres was examined. The first part of the study revealed significant changes both in the neurotransmitter level and in the enzyme activities; no correlation was observed, however, between the accumulation of GABA and the progression of the disease. In contrast, subsequent stages of HE in the TAA model were found to be characterized by a gradual decrease of both Bmax and KD values for GABA binding, which may reflect a gradual decrease in the number of binding sites, accompanied by sensitization of the remaining receptors. The results are discussed in view of the possible involvement of this inhibitory neurotransmitter in the pathogenesis of HE.
Wysmyk-Cybula
U
U
Dabrowiecki
Z
Z
Albrecht
J
J
D000612:4-Aminobutyrate Transaminase / Q000378:metabolism; D000081:Acetamides; D000818:Animals; D001921:Brain / Q000378:metabolism*; D002540:Cerebral Cortex / Q000201:enzymology; D003342:Corpus Striatum / Q000201:enzymology; D005260:Female; D006501:Hepatic Encephalopathy / Q000139:chemically induced*; D051381:Rats; D011919:Rats, Inbred Strains; D013570:Synaptic Membranes / Q000378:metabolism; D013853:Thioacetamide; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D000081:Acetamides; D013853:Thioacetamide; D005680:gamma-Aminobutyric Acid; D000612:4-Aminobutyrate Transaminase