Metabolism of amines in the isolated perfused mesenteric arterial bed of the rat.
1. Semicarbazide-sensitive amine oxidase (SSAO) activity has been demonstrated in the isolated mesenteric arterial bed of the rat in vitro by studying the metabolism of benzylamine (Bz) and tyramine (Tyr) added to the perfusing fluid. 2. Pretreatment of rats with (E)-2-(3',4'-dimethoxyphenyl)-3-fluoroallylamine (MDL72145), a potent inhibitor of SSAO in rat mesenteric blood vessels, reduced the amount of metabolites, following the addition of Bz (25 microM) or Tyr (100 microM) to the perfusing fluid, by 83% and 52% respectively. Inactivation of monoamine oxidase type A (MAO-A) by the addition of clorgyline (10 microM) to the perfusing fluid, had little effect on the appearance of metabolites from Tyr. 3. The presence of 3 microM cocaine in the perfusing fluid increased the amount of metabolites produced from Tyr. 4. The metabolites of Tyr appearing in the perfusion fluid from control preparations were 85% p-hydroxyphenylacetic and the remainder consisted of a mixture of p-hydroxyphenylacetaldehyde and, possible, p-hydroxyphenylethanol. 5. The metabolism of Tyr by homogenates of the rat mesenteric vascular bed was carried out by SSAO (60%) and MAO-A (40%) with very little contribution from MAO-B. Homogenates from rats pretreated with MDL 72145 showed metabolism of Tyr by MAO-A only. 6. These data indicate that SSAO is capable of metabolizing amines present in the fluid perfusing blood vessels to metabolites that are readily released. Histochemical evidence has shown that whereas MAO-A is present in the mitochondria of smooth muscle cells and nerve endings, SSAO is located in the plasma membrane of the smooth muscle cells. This subcellular distribution may explain the differences found between metabolites released from intact vessels and the metabolism seen in homogenates. The identity of the Tyr metabolizing activity in intact vessels that is resistant to both MDL 72145 and clorgyline remains to be determined.
Elliott
J
J
Department of Pharmacology, University of Cambridge.
Callingham
B A
BA
Sharman
D F
DF
D000818:Animals; D001679:Biogenic Amines / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D008638:Mesenteric Arteries / Q000378:metabolism; D008995:Monoamine Oxidase / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000201:enzymology / Q000378:metabolism*; D010477:Perfusion; D051381:Rats; D011919:Rats, Inbred Strains; D014439:Tyramine / Q000378:metabolism
D001679:Biogenic Amines; D008995:Monoamine Oxidase; D014439:Tyramine