Alterations of GABA-A and dopamine D-2 brain receptors in dogs with portal-systemic encephalopathy.
The binding characteristics of gamma-aminobutyric acid-A (GABA-A) receptors and the kinetic characteristics of the target enzyme of GABA synthesis in nerve terminals, glutamic acid decarboxylase (GAD), were studied in a dog model of portal-systemic encephalopathy obtained by porta-caval shunt performed in dimethylnitrosamine pretreated animals. Furthermore the properties of dopamine receptors and the levels of catecholamines of encephalopathic dogs were investigated. The mild stage of encephalopathy was characterized by an up-regulation of the inhibitory GABA-A receptors probably related to a decrese of GABA in nerve terminals since GAD was decreased and by a slight decrease of catecholamines and by an increased synthesis of octopamine associated with a decreased affinity of dopamine receptors. In the severe stage there was a selection of high affinity GABA-A receptors with an increased number of benzodiazepine recognition sites which were supersensitive to GABA stimulation, a decreased number of Dopamine D-2 receptors and a marked reduction of catecholamines. These data seem to suggest that the neurological disturbances of experimental portal-systemic encephalopathy might be the result of an imbalance between inhibitory and excitatory systems leading to a prevalence of the first one.
Zeneroli
M L
ML
Dipartimento di Scienze Farmaceutiche, Universita di Modena, Milan, Italy.
Baraldi
M
M
Ventura
E
E
Vezzelli
C
C
Tofanetti
O
O
Germini
M
M
Casciarri
I
I
D000818:Animals; D001921:Brain / Q000378:metabolism*; D003975:Diazepam / Q000378:metabolism; D004128:Dimethylnitrosamine / Q000633:toxicity; D004195:Disease Models, Animal; D004285:Dogs; D004298:Dopamine / Q000032:analysis; D005968:Glutamate Decarboxylase / Q000378:metabolism; D006501:Hepatic Encephalopathy / Q000139:chemically induced / Q000378:metabolism*; D007700:Kinetics; D009638:Norepinephrine / Q000032:analysis; D009655:Octopamine / Q000032:analysis; D011869:Radioligand Assay; D011954:Receptors, Dopamine / Q000378:metabolism*; D011963:Receptors, GABA-A / Q000378:metabolism*; D013569:Synapses / Q000201:enzymology
D011954:Receptors, Dopamine; D011963:Receptors, GABA-A; D009655:Octopamine; D005968:Glutamate Decarboxylase; D004128:Dimethylnitrosamine; D003975:Diazepam; D004298:Dopamine; D009638:Norepinephrine