Imidazolinic radioligands for the identification of hamster adipocyte alpha 2-adrenoceptors. 1989

J S Saulnier-Blache, and C Carpéné, and D Langin, and M Lafontan
I.N.S.E.R.M., Université Paul Sabatier, Toulouse, France.

Imidazolinic radioligands ([3H]UK 14304, [3H]idazoxan and [3H]RX 821002) were used for the identification of alpha 2-adrenoceptors on hamster fat cell membranes since there are limitations to the use of [3H]yohimbine and [3H]clonidine, which suggest alpha 2-adrenoceptor heterogeneity. Biological assays (lipolysis measurements) were performed on isolated fat cells and binding studies were carried out on fat cell membranes. The imidazolinic derivative, UK 14304, was a full agonist as compared to clonidine. Idazoxan and RX 821002 (2-(2-methoxy-1,4-benzodioxan-2yl)-2-imidazoline), a recently developed alpha 2-antagonist, were more potent alpha 2-antagonists than yohimbine in this fat cell model. [3H]UK 14304 was the most suitable agent for the quantification of the 'high-affinity state' alpha 2-adrenoceptors in binding studies since it did not exhibit the sensitivity to the composition of the buffer shown by [3H]clonidine. Although it is a potent alpha 2-antagonist, [3H]idazoxan had major limitations for use in the identification of alpha 2-adrenoceptors in this cell model since it also bound to 'non-adrenaline displaceable' binding sites which were revealed when imidazolinic derivatives (phentolamine) were used instead of adrenaline to determine the non-specific binding. We demonstrated that [3H]RX 821002 was a more suitable radioligand than [3H]yohimbine for labelling hamster fat cell alpha 2-adrenoceptors (KD = 1.0 +/- 0.1 nM, Bmax = 776 +/- 60 fmol/mg protein). Moreover, since it exhibited low affinity for 'imidazoline-preferring sites', it represents a valuable ligand even in tissues possessing such binding sites. We suggest that [3H]RX 821002 can be used to identify alpha 2-adrenoceptors in various tissues when these sites cannot be labelled with [3H]yohimbine.

UI MeSH Term Description Entries
D007093 Imidazoles Compounds containing 1,3-diazole, a five membered aromatic ring containing two nitrogen atoms separated by one of the carbons. Chemically reduced ones include IMIDAZOLINES and IMIDAZOLIDINES. Distinguish from 1,2-diazole (PYRAZOLES).
D007700 Kinetics The rate dynamics in chemical or physical systems.
D008066 Lipolysis The metabolic process of breaking down LIPIDS to release FREE FATTY ACIDS, the major oxidative fuel for the body. Lipolysis may involve dietary lipids in the DIGESTIVE TRACT, circulating lipids in the BLOOD, and stored lipids in the ADIPOSE TISSUE or the LIVER. A number of enzymes are involved in such lipid hydrolysis, such as LIPASE and LIPOPROTEIN LIPASE from various tissues. Lipolyses
D008297 Male Males
D008647 Mesocricetus A genus in the order Rodentia and family Cricetidae. One species, Mesocricetus auratus or golden hamster is widely used in biomedical research. Hamsters, Golden,Hamsters, Golden Syrian,Hamsters, Syrian,Mesocricetus auratus,Syrian Golden Hamster,Syrian Hamster,Golden Hamster,Golden Hamster, Syrian,Golden Hamsters,Golden Syrian Hamsters,Hamster, Golden,Hamster, Syrian,Hamster, Syrian Golden,Syrian Hamsters
D011810 Quinoxalines Quinoxaline
D011869 Radioligand Assay Quantitative determination of receptor (binding) proteins in body fluids or tissue using radioactively labeled binding reagents (e.g., antibodies, intracellular receptors, plasma binders). Protein-Binding Radioassay,Radioreceptor Assay,Assay, Radioligand,Assay, Radioreceptor,Assays, Radioligand,Assays, Radioreceptor,Protein Binding Radioassay,Protein-Binding Radioassays,Radioassay, Protein-Binding,Radioassays, Protein-Binding,Radioligand Assays,Radioreceptor Assays
D011942 Receptors, Adrenergic, alpha One of the two major pharmacological subdivisions of adrenergic receptors that were originally defined by the relative potencies of various adrenergic compounds. The alpha receptors were initially described as excitatory receptors that post-junctionally stimulate SMOOTH MUSCLE contraction. However, further analysis has revealed a more complex picture involving several alpha receptor subtypes and their involvement in feedback regulation. Adrenergic alpha-Receptor,Adrenergic alpha-Receptors,Receptors, alpha-Adrenergic,alpha-Adrenergic Receptor,alpha-Adrenergic Receptors,Receptor, Adrenergic, alpha,Adrenergic alpha Receptor,Adrenergic alpha Receptors,Receptor, alpha-Adrenergic,Receptors, alpha Adrenergic,alpha Adrenergic Receptor,alpha Adrenergic Receptors,alpha-Receptor, Adrenergic,alpha-Receptors, Adrenergic
D003000 Clonidine An imidazoline sympatholytic agent that stimulates ALPHA-2 ADRENERGIC RECEPTORS and central IMIDAZOLINE RECEPTORS. It is commonly used in the management of HYPERTENSION. Catapres,Catapresan,Catapressan,Chlophazolin,Clofelin,Clofenil,Clonidine Dihydrochloride,Clonidine Hydrochloride,Clonidine Monohydrobromide,Clonidine Monohydrochloride,Clopheline,Dixarit,Gemiton,Hemiton,Isoglaucon,Klofelin,Klofenil,M-5041T,ST-155,Dihydrochloride, Clonidine,Hydrochloride, Clonidine,M 5041T,M5041T,Monohydrobromide, Clonidine,Monohydrochloride, Clonidine,ST 155,ST155
D004146 Dioxanes Compounds that contain the structure 1,4-dioxane.

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