Benzodiazepine receptor-dependent modulation of neutrophil (PMN) free amino- and ?-keto acid profiles or immune functions

Abstract

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.

Early-stage 11C-Flumazenil PET predicts day-14 selective neuronal loss in a rodent model of transient focal cerebral ischemia

“…To our knowledge, the in vitro binding of flumazenil (previously known as Ro-151788) to leukocytes has not been reported so far. However, in one study, 45 consistent with previous work, 46,47 FMZ exerted no effect on a wide array of immune markers of neutrophils, suggesting it does not meaningfully bind to leukocytes. This probably reflects the fact that, in sharp contrast with benzodiazepines, FMZ is a specific ligand of the central BZR and as such has no affinity for the so-called “peripheral’” BZR (also called TSPO), 48,49 which is heavily expressed in post-stroke immune and inflammatory processes, 50 including neutrophil migration and adhesion.…”

Differential Expression of the 18 kDa Translocator Protein (TSPO) by Neoplastic and Inflammatory Cells in Mouse Tumors of Breast Cancer

“…However, it can be noted, in all three cases, that there is some expression of the murine TSPO in cells that are not F4/80 positive. Previous studies have reported that other inflammatory cells such as T cells, 41 monocytes 42,43 and neutrophils 42,44 can also express TSPO. For example, in a representative MCF-7 tumor tissue section (Appendix, Figure A3), some TSPO expression (green) can be seen in T-cells that are positively stained for CD3 (red).…”

A certain concentration of vecuronium and pipecuronium can inhibit the expression of neutrophils CD11b in human isolated venous blood

“…However, decrease peripheral blood neutrophils macrophages breathing outbreak. [7] Drugs can directly or indirectly affect intracellular Ca2 + regulation of cellular function, and Nishina K et al found that intravenous anesthetics may reduce neutrophil function by reducing intracellular Ca2 + concentration. [8] The mechanism of action may be that intravenous anesthetics, by virtue of their high lipid solubility, accumulate on the cell membrane, change the physical structure of the membrane, and cause the membrane enzyme action, especially the inhibition of protein kinase C, to change the cell function.…”