Binding of ( sup 3 H)idazoxan and of its methoxy derivative ( sup 3 H) RX821002 in human fat cells: ( sup 3 H)idazoxan but not ( sup 3 H) RX821002 labels additional non-alpha 2-adrenergic binding sites

Journal Article · Fri Jun 01 04:00:00 EDT 1990 · Molecular Pharmacology; (USA)

OSTI ID:6643880

Langin, D; Paris, H; Lafontan, M ^[1]

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1. Universite Paul Sabatier, Toulouse (France)

Binding studies were carried out in human fat cell membranes with two alpha 2-adrenergic antagonists, (3H)idazoxan and its methoxy derivative (3H)RX821002. Inhibition studies with epinephrine enantiomers indicate that (3H)RX821002 only binds to alpha 2-adrenoceptors, whereas (3H)idazoxan labels alpha 2-adrenoceptors and additional nonadrenergic sites (NAIBS). NAIBS and alpha 2-adrenoceptors display different affinities towards drugs from various chemical families. Imidazoline and some guanidine derivatives exhibit a high affinity for NAIBS. Pharmacological studies of human NAIBS indicate that they are slightly different from those previously reported in the rabbit, suggesting the existence of several subtypes of NAIBS. Furthermore, NAIBS are different from the previously described imidazoline-preferring sites. (3H)idazoxan and (3H)RX821002 saturation analyses were performed in human adipocytes from different anatomical locations, in order to compare the number of NAIBS and alpha 2-adrenoceptors. Although there was an important variation in NAIBS and alpha 2-adrenoceptor numbers in the studied samples, a very poor correlation was obtained between the Bmax values of the two sites. Moreover, alkylation of alpha 2-adrenoceptors by phenoxybenzamine produces a 90% reduction in accessible (3H)RX821002 binding sites, without modification of (3H)idazoxan binding. These data show that NAIBS are not closely related to the alpha 2-adrenergic molecule. In addition, benextramine appears to be a reversible competitor at NAIBS. (3H)idazoxan binding, but not (3H)RX821002 binding, is sensitive to K+, suggesting that the domains involved in the ligand-NAIBS interaction are different from those involved in the ligand-alpha 2-adrenoceptor interaction.

• OSTI ID: 6643880
• Journal Information: Molecular Pharmacology; (USA), Journal Name: Molecular Pharmacology; (USA) Vol. 37:6; ISSN 0026-895X; ISSN MOPMA
• Country of Publication: United States
• Language: English

Related Subjects

550201* -- Biochemistry-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
ADIPOSE TISSUE
ADRENAL HORMONES
ADRENALINE
ANIMAL CELLS
ANIMAL TISSUES
ANIMALS
AUTONOMIC NERVOUS SYSTEM AGENTS
BIOCHEMICAL REACTION KINETICS
BODY
CARDIOTONICS
CARDIOVASCULAR AGENTS
CELL CONSTITUENTS
CELL MEMBRANES
CONNECTIVE TISSUE
CONNECTIVE TISSUE CELLS
DRUGS
FAT CELLS
HYDROGEN COMPOUNDS
ISOTOPE APPLICATIONS
KINETICS
LABELLING
MAMMALS
MAN
MEMBRANE PROTEINS
MEMBRANES
NEUROREGULATORS
ORGANIC COMPOUNDS
PARASYMPATHOLYTICS
PARASYMPATHOMIMETICS
PRIMATES
PROTEINS
REACTION KINETICS
RECEPTORS
SOMATIC CELLS
SYMPATHOMIMETICS
TISSUES
TRACER TECHNIQUES
TRITIUM COMPOUNDS
VERTEBRATES