Benzodiazepine receptor-dependent modulation of neutrophil (PMN) free amino- and alpha-keto acid profiles or immune functions.
We have examined the effects of midazolam, Ro 5-4864 (agonist for "peripheral" [p] benzodiazepine receptors [BR]), PK 11195 (antagonist for pBR), flumazenil (antagonist for "central" BR), naloxone (antagonist for opiate receptors) and the combination of midazolam and Ro 5-4864, PK 11195, flumazenil or naloxone on intracellular amino- and alpha-keto acids and the immune function markers superoxide anion (O(2)(-)), hydrogen peroxide (H(2)O(2)) and released myeloperoxidase (MPO) activity in neutrophils (PMN). Only midazolam and Ro 5-4864 led to significant changes in the dynamic PMN free amino- and alpha-keto acid pools. Concerning PMN immune function markers, midazolam and Ro 5-4864 significantly decreased O(2)(-) and H(2)O(2) formation and released MPO. When midazolam and Ro 5-4864 were applied together they appeared to act additively. Pre-incubation with PK 11195 partially neutralized the midazolam effects whereas flumazenil or naloxone showed no effects. We therefore believe that pBR are involved in the signal transmission of anesthetic-induced cellular metabolic changes in PMN.
Mühling
J
J
Department of Anaesthesiology, Intensive Care Medicine, Pain Therapy, University Hospital, Justus Liebig University, 35385 Giessen, Germany. joerg.muehling@chiru.med.uni-giessen.de
Gonter
J
J
Nickolaus
K A
KA
Matejec
R
R
Welters
I D
ID
Wolff
M
M
Sablotzki
A
A
Engel
J
J
Krüll
M
M
Menges
T
T
Fuchs
M
M
Dehne
M G
MG
Hempelmann
G
G
D000328:Adult; D000596:Amino Acids / Q000378:metabolism*; D001570:Benzodiazepinones / Q000494:pharmacology; D002478:Cells, Cultured; D005442:Flumazenil / Q000494:pharmacology; D018757:GABA Modulators / Q000494:pharmacology; D058785:GABA-A Receptor Agonists; D058787:GABA-A Receptor Antagonists; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D007546:Isoquinolines / Q000494:pharmacology; D007651:Keto Acids / Q000378:metabolism*; D008297:Male; D008874:Midazolam / Q000494:pharmacology; D009270:Naloxone / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism*; D009195:Peroxidase / Q000187:drug effects / Q000378:metabolism; D011963:Receptors, GABA-A / Q000187:drug effects / Q000378:metabolism*; D013481:Superoxides / Q000378:metabolism
D000596:Amino Acids; D001570:Benzodiazepinones; D018757:GABA Modulators; D058785:GABA-A Receptor Agonists; D058787:GABA-A Receptor Antagonists; D007546:Isoquinolines; D007651:Keto Acids; D011963:Receptors, GABA-A; D013481:Superoxides; C028513:4'-chlorodiazepam; D009270:Naloxone; D005442:Flumazenil; D006861:Hydrogen Peroxide; D009195:Peroxidase; D008874:Midazolam; C037850:PK 11195