Augmented sensitivity to benzodiazepine in septic shock rats.
The purpose of this study was to assess the pharmacological characteristics of the benzodiazepine binding site in the brain of septic animals. We induced endotoxin shock in rats using a caecum ligation and puncture model. Following examination of the physiological state of the rats 24 hr after the caecum ligation and puncture, brain tissue samples were prepared for biochemical assay of amino acids and for the [3H]-diazepam radioligand binding assay. Amino acids assays indicated that the concentration of aromatic amino acids was higher in the CLP group (P< 0.05), the branched chain amino acid concentration was lower in the CLP group (P< 0.05) and the sulfur-containing amino acid concentration was elevated in the CLP group (P< 0.05) than in both the control and the sham-operated groups. [3H]-diazepam radioligand binding assays demonstrated that the number of receptors in the septic rats was increased in the forebrain (CLP rats; 2.37 +/- 0.04 pmol x mg(-1) protein, control rats; 1.45 +/- 0.02 pmol x mg(-1) protein, sham-operated rats; 1.49 +/- 0.03 pmol x mg(-1) protein), cerebellum (CLP rats; 1.55 +/- 0.05 pmol x mg(-1) protein, control rats; 1.05 +/- 0.02 pmol x mg(-1) protein, sham-operated rats: 1.09 +/- 0.02 pmol x mg(-1) protein) and brain stem (CLP rats; 1.21 +/- 0.04 pmol x mg(-1) protein, control rats; 0.61 +/- 0.02 pmol x mg(-1) protein, sham-operated rats; 0.63 +/- 0.02 pmol x mg(-1) protein) compared with the control and sham-operated rats (P< 0.05). In conclusion, it was considered that the increased number of benzodiazepine receptors may be one cause of the neuronal alteration observed in septic shock animals.
Komatsubara
T
T
Department of Anesthesiology and Reanimatology, Gunma University School of Medicine, Maebashi, Japan.
Kadoi
Y
Y
Saito
S
S
D000596:Amino Acids / Q000097:blood; D000818:Animals; D001923:Brain Chemistry; D003975:Diazepam / Q000378:metabolism; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D011963:Receptors, GABA-A / Q000032:analysis*; D012772:Shock, Septic / Q000378:metabolism*
D000596:Amino Acids; D011963:Receptors, GABA-A; D003975:Diazepam