The influence of monoamine oxidase activity on the release of noradrenaline by tyramine.
The influence of monoamine oxidase (MAO) activity on the kinetic characteristics of noradrenaline (NA) release evoked by tyramine has been examined. Dog splenic artery strips were incubated with [3H]NA after inhibition of catechol-O-methyl-transferase (COMT) and of extraneuronal uptake. In some experiments MAO was also inhibited. The strips were then perifused for 200 min. Some strips were exposed to tyramine (1.5, 40 and 3240 mumols L-1) from the 100th to the 200th min of perifusion. In control experiments (i.e. in the absence of tyramine) most of the [3H]NA accumulated in the strips (83% of tissue activity) and did not contribute to the efflux. The value of this "bound fraction" (the NA located at a site(s) from which it could not be displaced by a simple concentration gradient) was the same whether or not MAO was inhibited. At all concentrations, tyramine mobilized only one NA compartment. Increasing the concentration of tyramine resulted in a decrease of the "bound fraction", which became negligible for the highest concentration of tyramine used (3240 mumols L-1), regardless of MAO being inhibited or not. However, for the lower concentrations of tyramine, MAO inhibition resulted in an increase in the amine's releasing effect. The formation of 3,4-dihydroxy-phenylglycol (DOPEG) increased with increase of tyramine from the 1.5 to 40 mumols L-1 concentration, but not beyond. The ratio NA/DOPEG increased for all concentrations of tyramine. Thus, it was not possible to exclude an inhibitory effect of tyramine on MAO activity with the highest concentration used.
Brandão
F
F
Laboratório de Farmacologia, Faculdade de Medicina, Porto, Portugal.
Araújo
D
D
Monteriro
J G
JG
D000818:Animals; D004285:Dogs; D066298:In Vitro Techniques; D008734:Methoxyhydroxyphenylglycol / Q000031:analogs & derivatives / Q000378:metabolism; D008995:Monoamine Oxidase / Q000378:metabolism*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism*; D009638:Norepinephrine / Q000378:metabolism*; D013157:Splenic Artery / Q000187:drug effects / Q000378:metabolism; D014439:Tyramine / Q000494:pharmacology*
D008734:Methoxyhydroxyphenylglycol; D008995:Monoamine Oxidase; C010117:3,4-dihydroxyphenylglycol; D009638:Norepinephrine; D014439:Tyramine