The release of 3H-noradrenaline by p- and m-tyramines and -octopamines, and the effect of deuterium substitution in alpha-position

Abstract

The 3H-noradrenaline-releasing effects of p- and m-tyramines and -octopamines, either deuterated or not, were studied in isolated vasa deferentia of the rat (COMT inhibited and calcium-free solution in all experiments). Km for uptake1 was higher for octopamines than for tyramines, but not increased by the introduction of deuterium in alpha-position, except for (probably contaminated) deuterated p-octopamine. Other tissues were preloaded with 3H-noradrenaline. After inhibition of vesicular uptake and MAO equi-releasing concentrations of the eight amines were strictly correlated with Km, they were 6 to 7 times higher for unsubstituted octopamines than for corresponding tyramines. When only MAO (but not vesicular uptake) was inhibited, this difference decreased to about 4-fold, but the releasing potency of the deuterated amines (relative to their parent amines) remained unchanged (except for p-octopamine). When vesicular uptake and MAO were intact, unsubstituted octopamines were only 1.5 to 2.2 times less potent than the corresponding tyramines. Analysis of the efflux of 3H-DOPEG confirmed that this gain in the relative potencies of octopamines is due to their increased ability to mobilize vesicular 3H-noradrenaline; moreover, deuterated amines as well were then better mobilizers than were their parent amines. It is concluded that, provided vesicular uptake is intact, the introduction of a beta-OH-group enhances the ability of indirectly acting sympathomimetic amines to mobilize vesicular noradrenaline; the introduction of deuterium in alpha-position, on the other hand, enhances this mobilizing effect exclusively when MAO is intact.