Inhibition of amine oxidase activity by derivatives that recognize imidazoline I2 sites.
Nonadrenergic imidazoline binding sites (imidazoline I2 sites) have been described to be colocated with monoamine oxidase (MAO) in the mitochondrial fraction of various cell types. In the present work, the authors considered whether this colocation could be associated with a functional interplay. In rat liver membranes, [3H]-idazoxan binding to I2 receptors was competed for by naphazoline and idazoxan, which also shared a high affinity for alpha-2 adrenoceptors (alpha-2 ARs). The chemicals 2-n-heptylimidazoline (S 15430), 1-methyl-5-n-heptylimidazole (S 15674), 2-benzofuran-2-yl-imidazoline (RX 801077) and 2-(1,3-benzodioxanyl)-2-imidazoline (RX 821029) exhibited higher affinity for I2 receptors than for alpha-2 ARs. The most selective agent was S 15430 with a 150-fold higher affinity for liver I2 receptors than for adipocyte alpha-2 ARs. Moreover, [3H]-idazoxan binding was also competed for by several MAO inhibitors (MAOI) that are not imidazoline or guanidinium derivatives such as tranylcypromine, harmaline, clorgiline and pargyline. Rat liver MAO activity was not only inhibited by MAOIs but also by some imidazoline derivatives: cirazoline, naphazoline, S 15674, RX 801077 and RX 821029. Idazoxan had no effect on MAO activity; it neither inhibited MAO nor prevented the inhibition induced by other imidazolines or MAOIs. This suggested that the ligand recognition site of I2 receptors was distinct from the MAOI target site. Furthermore, some imidazolines inhibited the activity of bovine plasma amine oxidase, an enzyme that does not possess the same cofactor as MAO and is insensitive to harmaline or pargyline.(ABSTRACT TRUNCATED AT 250 WORDS)
Carpéné
C
C
Institut National de la Santé et de la Recherche Médicale (INSERM U 317), Institut Louis Bugnard, Université Paul Sabatier, Toulouse, France.
Collon
P
P
Remaury
A
A
Cordi
A
A
Hudson
A
A
Nutt
D
D
Lafontan
M
M
D006631:Amine Oxidase (Copper-Containing); D000818:Animals; D001665:Binding Sites; D001667:Binding, Competitive; D006224:Cricetinae; D004146:Dioxanes / Q000378:metabolism; D019329:Idazoxan / Q000031:analogs & derivatives; D007093:Imidazoles / Q000494:pharmacology*; D054755:Imidazoline Receptors; D008297:Male; D008647:Mesocricetus; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology*; D000587:Oxidoreductases Acting on CH-NH Group Donors / Q000037:antagonists & inhibitors*; D051381:Rats; D017208:Rats, Wistar; D018341:Receptors, Adrenergic, alpha-2 / Q000187:drug effects; D011955:Receptors, Drug / Q000378:metabolism*
D004146:Dioxanes; D007093:Imidazoles; D054755:Imidazoline Receptors; D008996:Monoamine Oxidase Inhibitors; D018341:Receptors, Adrenergic, alpha-2; D011955:Receptors, Drug; C058525:2-methoxyidazoxan; D006631:Amine Oxidase (Copper-Containing); D000587:Oxidoreductases Acting on CH-NH Group Donors; D019329:Idazoxan