Benzodiazepine receptor-dependent modulation of neutrophil (PMN) free amino- and ?-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 α-keto acids and the immune function markers superoxide anion (O^sub 2^^sup -^), hydrogen peroxide (H^sub 2^O^sub 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 α-keto acid pools. Concerning PMN immune function markers, midazolam and Ro 5-4864 significantly decreased O^sub 2^^sup -^ and H^sub 2^O^sub 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.[PUBLICATION ABSTRACT]