Resistance to 3-mercaptopropionic acid-induced seizures in hepatic encephalopathy.
OBJECTIVE
To determine if a model of hepatic encephalopathy (HE) exhibits decreased sensitivity to the neuronal effects of a drug that induces seizures as a consequence of decreasing GABA-mediated inhibitory neurotransmission.


METHODS
3-Mercaptopropionic Acid (MPA) is an inhibitor of L-glutamate decarboxylase which catalyzes the synthesis of GABA from glutamate. MPA was administered, either by intraperitoneal or intracerebroventricular injection, into rats with stage III HE due to thioacetamide-induced fulminant hepatic failure and into normal control rats.


RESULTS
When MPA was administered by intraperitoneal injection, seizure-inducing doses were similar for rats with HE and control rats. However, when a constant dose of MPA (330 micrograms) was administered by intracerebroventricular injection, rats with HE took significantly longer to develop seizures than control rats (16.2 vs. 7.3 minutes; p < 0.0005).


CONCLUSIONS
In a model of HE: (i) There is increased resistance to the convulsive effects of MPA; and (ii) This phenomenon is apparent when MPA is given centrally, but not when it is given peripherally. Increased resistance to the development of a complication of reduced GABA-mediated neurotransmission induced by MPA in the model provides support for the hypothesis that HE is associated with increased GABA-mediated inhibitory neurotransmission.
Ferreira
M R
MR
Liver Diseases Section, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland, USA.
Gammal
S H
SH
Jones
E A
EA
D015097:3-Mercaptopropionic Acid / Q000008:administration & dosage; D000818:Animals; D003292:Convulsants / Q000008:administration & dosage; D005968:Glutamate Decarboxylase / Q000037:antagonists & inhibitors; D006501:Hepatic Encephalopathy / Q000150:complications / Q000378:metabolism / Q000503:physiopathology*; D007274:Injections, Intraperitoneal; D007276:Injections, Intraventricular; D051381:Rats; D017207:Rats, Sprague-Dawley; D012640:Seizures / Q000139:chemically induced / Q000150:complications / Q000503:physiopathology*; D009435:Synaptic Transmission; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D003292:Convulsants; D005680:gamma-Aminobutyric Acid; D015097:3-Mercaptopropionic Acid; D005968:Glutamate Decarboxylase