Kynurenic acid influences the respiratory parameters of rat heart mitochondria.
In the present study the effect of L-kynurenine, kynurenic acid and quinolinic acid on the heart mitochondrial function were investigated. Mitochondria were incubated with saturating concentrations of respiratory substrates glutamate/malate (5 mmol/l), succinate (10 mmol/l) or NADH (1 mmol/l), with and without kynurenines. The concentration of kynurenines varied between 1.25 micromol/l and 10 mmol/l. From all investigated kynurenines, only kynurenic acid affected dose-dependently the respiratory parameters of heart mitochondria. Respiratory control and P/O values were reduced significantly with glutamate/malate and moderately with succinate as substrates in the presence of 125 micromol/l to 10 mmol/l kynurenic acid. A known elevation of L-kynurenine in the blood of patients with ischemic heart disease or essential hypertension may suggest the involvement of L-kynurenine metabolites in the impairment of heart mitochondrial function, for example in cardiomyopathy.
Baran
H
H
Institute of Pharmacology and Toxicology, Veterinary University Vienna, Austria. Halina.Baran@svu-wien.ac.at
Staniek
K
K
Kepplinger
B
B
Gille
L
L
Stolze
K
K
Nohl
H
H
D000818:Animals; D019069:Cell Respiration / Q000187:drug effects / Q000502:physiology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D018698:Glutamic Acid / Q000494:pharmacology; D007736:Kynurenic Acid / Q000494:pharmacology*; D007737:Kynurenine / Q000494:pharmacology*; D008293:Malates / Q000494:pharmacology; D008297:Male; D008929:Mitochondria, Heart / Q000187:drug effects* / Q000502:physiology; D010101:Oxygen Consumption / Q000187:drug effects* / Q000502:physiology; D017378:Quinolinic Acid / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley
D018691:Excitatory Amino Acid Antagonists; D008293:Malates; D007737:Kynurenine; D018698:Glutamic Acid; C030298:malic acid; D017378:Quinolinic Acid; D007736:Kynurenic Acid