Imidazoline binding sites in fat cells. Localization and pharmacologic differentiation from alpha 2-adrenergic...

Studies were carried out to define the cellular distribution and pharmacologic properties of the nonadrenergic [3H]idazoxan binding sites in white fat cells from various species (the term "nonadrenergic [3H]idazoxan binding sites" [NAIBS] has been retained pending a final decision about their name). NAIBS having quite similar binding properties were found in human, rat, hamster, rabbit, and dog fat cells. NAIBS are located both in plasma membranes (25 to 35%) and in intracellular membranes corresponding to the crude mitochondrial fraction of adipose tissue (65 to 75% of the total number of NAIBS found in the particulate fraction), while alpha 2-adrenergic receptors are exclusively located on the plasma membrane. NAIBS have no affinity for catecholamines but have a noticeable affinity for some imidazolinic and guanidinic derivatives. NAIBS are different from the "imidazoline receptors" which bind [3H]para-aminoclonidine in central nervous system areas. A comparative structure affinity study was performed to delineate the respective affinities of various imidazoline derivatives towards NAIBS and alpha 2-adrenergic receptors and to try to find selective ligands for both sites. Binding properties of the two sites were clearly different. Moreover, chronic administration of idazoxan and RX821002 to adult rabbits (4 mg/kg, subcutaneously for 7 days), resulted in an up-regulation of alpha 2-adrenoceptors in fat cells while the number of NAIBS was unaffected by the treatment. There is no clear demonstration of an interaction between NAIBS and G-proteins, adenylate cyclase, or lipolytic function in fat cells. Further studies are required to define their putative role in fat cells.