Discrimination between alpha 2-adrenoceptors and [3H]idazoxan-labelled non-adrenergic sites in rabbit white fat cells.
Previous results indicated that the rabbit could represent a suitable model for investigations on the functional role of alpha 2-adrenoceptors in fat cells, but the characterization of these receptors was not resolved yet. In the present report, imidazoline compounds were used to attempt a better definition of rabbit adipocyte alpha 2-receptivity by means of lipolysis and binding studies. Lipolysis data showed that UK14304 is a full alpha 2-adrenoceptor agonist promoting a strong antilipolysis in rabbit fat cells. Moreover, the methoxy derivative of idazoxan, RX821002, is a more potent antagonist of UK14304-induced antilipolysis than idazoxan or yohimbine. Whereas [3H]yohimbine failed to bind at rabbit adipocyte alpha 2-adrenoceptors, [3H]UK14304 and [3H]RX821002 are valuable tools to study this receptor. Analysis of binding data demonstrated that [3H]UK14304 labels the high-affinity-state receptor while [3H]RX821002 binds to the whole alpha 2-adrenergic population. Inhibition studies of [3H]RX821002 and [3H]UK14304 binding by various compounds confirmed the alpha 2-adrenergic nature of the sites labelled by both radioligands. The other alpha 2-adrenoceptor radioligand, [3H]idazoxan, labelled binding sites which are insensitive to catecholamines. Competition studies of [3H]idazoxan binding with imidazoline derivatives revealed structure-activity relationships different from those of alpha 2-adrenoceptors. The most striking observation is that substitutions in the 2-position of idazoxan markedly reduce the affinity for the non-adrenergic sites, whereas the alpha 2-potency is increased or unchanged.
Langin
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D
INSERM, U-317, Université Paul Sabatier, Toulouse, France.
Paris
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H
Dauzats
M
M
Lafontan
M
M
D000273:Adipose Tissue / Q000166:cytology / Q000378:metabolism*; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000818:Animals; D001667:Binding, Competitive / Q000187:drug effects; D000068438:Brimonidine Tartrate; D004146:Dioxanes / Q000494:pharmacology*; D004147:Dioxins / Q000494:pharmacology*; D004837:Epinephrine / Q000494:pharmacology; D019329:Idazoxan / Q000031:analogs & derivatives; D066298:In Vitro Techniques; D007700:Kinetics; D008066:Lipolysis / Q000187:drug effects; D008297:Male; D011810:Quinoxalines / Q000494:pharmacology; D011817:Rabbits; D011869:Radioligand Assay; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects*; D011955:Receptors, Drug / Q000187:drug effects*; D013329:Structure-Activity Relationship
D000317:Adrenergic alpha-Antagonists; D004146:Dioxanes; D004147:Dioxins; D011810:Quinoxalines; D011942:Receptors, Adrenergic, alpha; D011955:Receptors, Drug; D000068438:Brimonidine Tartrate; C058525:2-methoxyidazoxan; D019329:Idazoxan; D004837:Epinephrine