Die Verstärkung der Noradrenalinwirkung durch Tyramin

Summary

Rat atria were isolated and suspended in Tyrode solution at 32°C. The action of tyramine on force of contraction and spontaneous rate was investigated and dose-response curves were plotted for concentrations of 10⁻⁸ to 10⁻⁴ g/ml. In another series of experiments atria obtained from rats treated with reserpine were exposed to varying concentrations of tyramine (10⁻⁷ to 10⁻⁵ g/ml) which had lost their heart stimulating properties. Dose-response curves for rate and force of contraction were obtained with noradrenaline concentrations ranging from 10⁻¹¹ to 10⁻⁵g/ml. Tyramine caused a graded parallel shift of the curves to the left, thus indicating an enhancement of the noradrenaline action. The schedule of reserpine treatment did not cause supersensitivity toward noradrenaline which therefore did not interfere with the assessment of noradrenaline tyramine interactions. The experimental conditions excluded further the possibility that noradrenaline was first taken up and then released by the tyramine.

The dose-response curves of tyramine on normal atria corresponded well to those obtained on atria of reserpine-treated rats if in the latter experiments noradrenaline concentrations of 10⁻⁹ to 10⁻⁸ were present. According to several authors noradrenaline concentrations of this order of magnitude have been found in the perfusate or blood leaving organs stimulated with tyramine. Therefore, the shift by tyramine of the dose response curves of noradrenaline to the left is likely to occur with released noradrenaline as well and this would result in subthreshold amounts of noradrenaline becoming very effective indeed.

It is suggested that the powerful sympathomimetic effects of indirectly acting amines may be explained by a combination of their properties to release noradrenaline and to inhibit its removal at the same time which would result in potentiation of the noradrenaline actions.