Changes in the status of neurotransmitter receptors in a rabbit model of hepatic encephalopathy.

Abstract

It has previously been shown in an animal model of hepatic encephalopathy (HE) that the number of receptors for the inhibitory neurotransmitter, gamma-aminobutyric acid (GABA), increases and that the number of receptors for the excitatory neurotransmitter, glutamate, decreases. To determine the functional status of other neurotransmitter systems in HE, measurements were made of the specific binding of other neurotransmitters to synaptic membranes prepared from the brains of normal rabbits and rabbits in HE due to galactosamine-induced acute liver failure. The development of HE was associated with: (i) a decrease in the density (Bmax) of receptors for the two excitatory amino acid neurotransmitters, aspartate and kainic acid; (ii) an increase in the Bmax of both the low and high affinity binding site for strychnine, a marker for the inhibitory neurotransmitter glycine; (iii) a decrease in the affinity (Kd) of receptors for dopamine, and (iv) no appreciable change in either the specific binding of [3H]D-ala2-methionine enkephalinamide or [3H]naloxone, markers for opiate receptors, or in the Bmax or the Kd of receptors for acetylcholine. If it is assumed that the sensitivity of the brain to neurotransmitters varies directly with the density of neurotransmitter receptors, HE may be associated with increased sensitivity to inhibitory amino acid neurotransmitters and decreased sensitivity to excitatory amino acid neurotransmitters. Thus, the observed changes in neurotransmitter receptors in HE afford a feasible pathophysiological basis for the mediation of the neural inhibition of HE.