Relationship between I2 imidazoline binding sites and monoamine oxidase B in liver.
Biochemical and pharmacologic studies suggest that I2 imidazoline binding sites (I2BS) represent a heterogeneous family of membrane proteins. Indeed, the imidazoline binding sites located on monoamine oxidases (MAO) A and B display different pharmacologic properties. Recent results suggest that in liver and brain, I2BS may be located on proteins distinct from MAOs. The following observations indicate that in liver and brain, [3H]idazoxan binds exclusively to I2BS located on MAO-B: (1) size exclusion chromatography of digitonin-solubilized preparations from rabbit and human liver showed that [3H]idazoxan-specific binding eluted only in two peaks (approximately 175,000 and approximately 100,000 Da, corresponding to 90% and 10% of the recovered [3H]idazoxan binding) which also contained MAOs as determined by [14C]tyramine oxidation and Western blot analysis; (2) according to previous results obtained in various human and rat tissues, experiments performed in mice liver and brain showed that idazoxan was a potent inhibitor of [125I]-AZIPI photoincorporation to MAO-B but not to MAO-A; (3) in MAO-deficient transgenic mice, [3H]idazoxan binding to liver and brain membranes was completely abolished in MAO-B knockout mice and was not affected in MAO-A knockout mice. Together, these results show that in both liver and brain, I2BS are located exclusively on MAO-B. The imidazoline binding site on MAO-A, which photoincorporates [125I]-AZIPI and displays a low affinity for idazoxan, may not belong to the family of the I2 imidazoline binding sites.
I.N.S.E.R.M. U.388 Pharmacologie Moléculaire et Physiopathologie rénale, Institut Louis Bugnard, C.H.U. Rangeuil, Toulouse, France.
A
A
Remaury
C
C
Ordener
J
J
Shih
A
A
Parini
D000818:Animals; D001665:Binding Sites; D006801:Humans; D019329:Idazoxan / Q000378:metabolism; D054755:Imidazoline Receptors; D007527:Isoenzymes / Q000378:metabolism; D007700:Kinetics; D008099:Liver / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D008995:Monoamine Oxidase / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D011817:Rabbits; D051381:Rats; D011955:Receptors, Drug / Q000378:metabolism*; D014439:Tyramine / Q000378:metabolism
D054755:Imidazoline Receptors; D007527:Isoenzymes; D011955:Receptors, Drug; D008995:Monoamine Oxidase; D014439:Tyramine; D019329:Idazoxan