Brain gamma-aminobutyric acid receptor binding is normal in rats with thioacetamide-induced hepatic encephalopathy despite elevated plasma gamma-aminobutyric acid-like activity.
Brain gamma-aminobutyric acid (GABA) receptor density, affinity, and function, and plasma GABA-like activity were determined in rats with acute hepatic encephalopathy induced by an intraperitoneal injection of thioacetamide. In addition, the effect of various stress factors on brain GABA binding was assessed. Plasma GABA-like activity was significantly increased in rats with thioacetamide-induced hepatic encephalopathy compared with rats injected with vehicle alone (1506 +/- 993 nM, n = 7 vs. 367 +/- 97 nM, n = 9, mean +/- SD; p less than 0.001). In contrast, there were no alterations in either brain GABA receptor binding or in GABA-enhanced benzodiazepine binding in rats with hepatic encephalopathy when compared with relevant controls. However, rats that had received intraperitoneal injections of thioacetamide or vehicle (0.15 M NaCl) had significantly more low-affinity GABA receptors than rats that had neither been injected nor handled before killing (8769 +/- 1101 vs. 2710 +/- 757 fmol/mg protein, mean +/- SEM, p less than 0.001). We concluded that stress factors appear to be important causes of altered brain GABA binding. Brain GABA receptor binding and function, however, are unaltered in rats with thioacetamide-induced hepatic encephalopathy despite elevated plasma GABA-like activity.
Maddison
J E
JE
Department of Pharmacology, University of Sydney, Australia.
Dodd
P R
PR
Johnston
G A
GA
Farrell
G C
GC
D000818:Animals; D001665:Binding Sites; D001921:Brain / Q000378:metabolism*; D006501:Hepatic Encephalopathy / Q000139:chemically induced / Q000378:metabolism*; D008297:Male; D011869:Radioligand Assay; D051381:Rats; D011919:Rats, Inbred Strains; D011963:Receptors, GABA-A / Q000302:isolation & purification / Q000378:metabolism*; D013312:Stress, Physiological / Q000378:metabolism; D013853:Thioacetamide; D005680:gamma-Aminobutyric Acid / Q000097:blood*
D011963:Receptors, GABA-A; D013853:Thioacetamide; D005680:gamma-Aminobutyric Acid