Involvement of monoamine oxidase and noradrenaline uptake in the positive chronotropic effects of apigenin in rat atria.
In rat isolated atria spontaneously beating and labelled with [3H]noradrenaline, exposure to the flavonoid apigenin increased the atrial rate in a concentration-dependent manner (0.01-30 microM). This increase was accompanied by a reduction of 60% in the uptake of [3H]noradrenaline as well as by a modification in the pattern of [3H]noradrenaline and metabolites spontaneously released. Sixty minutes after exposure to 30 microM apigenin, the proportion of unmetabolized [3H]noradrenaline increased from 11% to 45% of the total products collected in the organ bath whereas the tritiated O-methylated deaminated metabolites decreased from 33% to 14% of the total efflux. A small but significant decrease in the outflow of [3H]3,4-dihydroxymandelic acid as well as a tendency to a decrease in the efflux of [3H]3,4-dihydroxyphenylglycol was also observed. Furthermore, apigenin inhibited in a concentration-dependent manner the activity of monoamine oxidase in the rat atrial homogenates. The calculated IC50 (7.7 microM) was within the range that produced 50% of the maximal increase in atrial rate. It is concluded that apigenin possesses the property to increase the atrial rate, probably as a result of a reduction in noradrenaline uptake as well as in monoamine oxidase activity.
Instituto de Investigaciones Farmacológicas, CONICET, Buenos Aires, Argentina. postmaster@invfar.edu.ar
P S
PS
Lorenzo
M C
MC
Rubio
J H
JH
Medina
E
E
Adler-Graschinsky
D000818:Animals; D016275:Atrial Function; D020843:Chamomile; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005260:Female; D005419:Flavonoids / Q000494:pharmacology*; D006325:Heart Atria / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D008995:Monoamine Oxidase / Q000378:metabolism*; D009638:Norepinephrine / Q000378:metabolism*; D009822:Oils, Volatile / Q000494:pharmacology*; D010946:Plants, Medicinal; D051381:Rats; D017208:Rats, Wistar; D014316:Tritium
D004791:Enzyme Inhibitors; D005419:Flavonoids; D009822:Oils, Volatile; D014316:Tritium; D008995:Monoamine Oxidase; D009638:Norepinephrine