Pathways involved in alanyl-glutamine-induced changes in neutrophil amino- and alpha-keto acid homeostasis or immunocompetence.
We examined the effects of DON [glutamine-analogue and inhibitor of glutamine-requiring enzymes], alanyl-glutamine (regarding its role in neutrophil immunonutrition) and alanyl-glutamine combined with L-NAME, SNAP, DON, beta-alanine and DFMO on neutrophil amino and alpha-keto acid concentrations or important neutrophil immune functions in order to establish whether an inhibitor of *NO-synthase [L-NAME], an *NO donor [SNAP], an analogue of taurine and a taurine transport antagonist [beta-alanine], an inhibitor of ornithine-decarboxylase [DFMO] as well as DON could influence any of the alanyl-glutamine-induced effects. In summary, irrespective of which pharmacological, metabolism-inhibiting or receptor-mediated mechanisms were involved, our results showed that impairment of granulocytic glutamine uptake, modulation of intracellular glutamine metabolisation and/or de novo synthesis as well as a blockade of important glutamine-dependent metabolic processes may led to significant modifications of physiological and immunological functions of the affected cells.
Mühling
J
J
Clinic of Anaesthesiology, University Hospital Giessen and Marburg, Justus-Liebig-University Giessen, Giessen, Federal Republic of Germany. joerg.muehling@chiru.med.unigiessen.de
Burchert
D
D
Langefeld
T W
TW
Matejec
R
R
Harbach
H
H
Engel
J
J
Wolff
M
M
Welters
I D
ID
Fuchs
M
M
Menges
T
T
Krüll
M
M
Hempelmann
G
G
D000328:Adult; D000596:Amino Acids / Q000737:chemistry / Q000378:metabolism*; D000903:Antibiotics, Antineoplastic / Q000378:metabolism; D003980:Diazooxonorleucine / Q000378:metabolism; D004151:Dipeptides / Q000378:metabolism*; D000518:Eflornithine / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000378:metabolism; D006706:Homeostasis; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D007121:Immunocompetence / Q000502:physiology*; D007651:Keto Acids / Q000737:chemistry / Q000378:metabolism*; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000378:metabolism; D009504:Neutrophils / Q000737:chemistry / Q000166:cytology / Q000378:metabolism*; D020030:Nitric Oxide Donors / Q000378:metabolism; D016877:Oxidants / Q000378:metabolism; D009195:Peroxidase / Q000378:metabolism; D026423:S-Nitroso-N-Acetylpenicillamine / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D013481:Superoxides / Q000378:metabolism
D000596:Amino Acids; D000903:Antibiotics, Antineoplastic; D004151:Dipeptides; D004791:Enzyme Inhibitors; D007651:Keto Acids; D020030:Nitric Oxide Donors; D016877:Oxidants; D003980:Diazooxonorleucine; D013481:Superoxides; D026423:S-Nitroso-N-Acetylpenicillamine; D006861:Hydrogen Peroxide; D009195:Peroxidase; C054122:alanylglutamine; D019331:NG-Nitroarginine Methyl Ester; D000518:Eflornithine