The release of 3H-noradrenaline by p- and m-tyramines and -octopamines, and the effect of deuterium substitution in alpha-position.
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.
Schönfeld
C L
CL
Institut für Pharmakologie und Toxikologie, Universität Würzburg, Federal Republic of Germany.
Trendelenburg
U
U
D015078:2-Hydroxyphenethylamine / Q000031:analogs & derivatives / Q000378:metabolism*; D000818:Animals; D002394:Catechol O-Methyltransferase / Q000378:metabolism; D003903:Deuterium; D007553:Isotope Labeling; D007700:Kinetics; D008297:Male; D008734:Methoxyhydroxyphenylglycol / Q000031:analogs & derivatives / Q000378:metabolism; D008995:Monoamine Oxidase / Q000378:metabolism; D009638:Norepinephrine / Q000378:metabolism*; D009655:Octopamine / Q000378:metabolism* / Q000031:analogs & derivatives; D010627:Phenethylamines / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D014316:Tritium; D014439:Tyramine / Q000378:metabolism*
D010627:Phenethylamines; D014316:Tritium; D009655:Octopamine; D008734:Methoxyhydroxyphenylglycol; D015078:2-Hydroxyphenethylamine; D003903:Deuterium; C005310:norfenefrine; D008995:Monoamine Oxidase; D002394:Catechol O-Methyltransferase; C010117:3,4-dihydroxyphenylglycol; D009638:Norepinephrine; D014439:Tyramine