Brandão F, Araújo D, Monteriro J G
Laboratório de Farmacologia, Faculdade de Medicina, Porto, Portugal.
J Pharm Pharmacol. 1989 Oct;41(10):729-32. doi: 10.1111/j.2042-7158.1989.tb06353.x.
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.
研究了单胺氧化酶（MAO）活性对酪胺诱发的去甲肾上腺素（NA）释放动力学特征的影响。在抑制儿茶酚-O-甲基转移酶（COMT）和神经外摄取后，用[3H]NA孵育犬脾动脉条。在一些实验中，MAO也被抑制。然后将这些条带灌流200分钟。在灌流的第100至200分钟，一些条带暴露于酪胺（1.5、40和3240μmol L-1）。在对照实验（即不存在酪胺）中，大部分[3H]NA积聚在条带中（占组织活性的83%），对流出没有贡献。无论MAO是否被抑制，这种“结合部分”（位于一个位点的NA，其不能被简单的浓度梯度所取代）的值是相同的。在所有浓度下，酪胺仅动员一个NA区室。酪胺浓度增加导致“结合部分”减少，对于所用的最高酪胺浓度（3240μmol L-1），无论MAO是否被抑制，“结合部分”都变得可以忽略不计。然而，对于较低浓度的酪胺，MAO抑制导致胺释放作用增强。随着酪胺浓度从1.5增加到40μmol L-1，3,4-二羟基苯乙二醇（DOPEG）的形成增加，但超过此浓度则不再增加。对于所有酪胺浓度，NA/DOPEG比值均增加。因此，无法排除所用最高浓度酪胺对MAO活性的抑制作用。
