Inhibition of mouse liver respiration by Chelidonium majus isoquinoline alkaloids.
The alkaloids from Chelidonium majus L. which had a significant inhibitory effect in mitochondrial respiration were those which contain a positive charge due to a quaternary nitrogen atom, i.e., chelerythrine, sanguinarine, berberine and coptisine, both with malate+glutamate or with succinate as substrates. When malate+glutamate was used as substrate, chelerythrine and berberine, which contain methoxy groups, were particularly more active, since they had a strong effect even at low concentrations. In submitochondrial particles, berberine and coptisine had a marked inhibitory effect on NADH dehydrogenase activity but practically no effect on succinate dehydrogenase activity, whereas chelerythrine and sanguinarine inhibited more strongly succinate dehydrogenase than NADH dehydrogenase, which is in agreement with the results found for mitochondrial respiration. Protopine and allocryptopine, which did not inhibit mitochondrial respiration, strongly inhibited NADH dehydrogenase in submitochondrial particles, but had no effect on succinate dehydrogenase activity.
Barreto
M Carmo
MC
Departamento de Ciências Tecnológicas e Desenvolvimento, Centro de Investigação de Recursos Naturais, Universidade dos Açores, Rua da Mãe de Deus, 9502 Ponta Delgada, Portugal. barreto@notes.uac.pt
Pinto
Ruy E
RE
Arrabaça
João D
JD
Pavão
M Leonor
ML
D000470:Alkaloids / Q000302:isolation & purification / Q000494:pharmacology*; D000818:Animals; D019069:Cell Respiration / Q000187:drug effects; D028281:Chelidonium / Q000737:chemistry*; D007546:Isoquinolines / Q000302:isolation & purification / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008930:Mitochondria, Liver / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D015394:Molecular Structure; D009245:NADH Dehydrogenase / Q000037:antagonists & inhibitors; D010100:Oxygen / Q000378:metabolism*; D013329:Structure-Activity Relationship; D013385:Succinate Dehydrogenase / Q000037:antagonists & inhibitors
D000470:Alkaloids; D007546:Isoquinolines; D013385:Succinate Dehydrogenase; D009245:NADH Dehydrogenase; C039109:isoquinoline; D010100:Oxygen