A1 ADENOSINE RECEPTORS IN THE HUMAN FAT-CELL - TISSUE DISTRIBUTION AND REGULATION OF RADIOLIGAND BINDING

Identification of adenosine A1 receptor binding sites was performed using the antagonist, [H-3]1,3-dipropyl-8-cyclopentyl-xanthine ([H-3]DPCPX), and the agonist [H-3](-)-N6-R-phenylisopropyladenosine ([H-3](-)-PIA) on human adipocyte membranes from different anatomical localizations (i.e. abdominal, femoral and omental fat deposits). Despite the strong antilipolytic effect initiated by various adenosine analogs, the human adipocytes were poorly equipped in adenosine A1 receptors whatever the anatomical location (B(max) less-than-or-equal-to 95 fmol/mg of protein for the antagonist [H-3]DPCPX and less-than-or-equal-to 72 fmol/mg for the agonist [H-3](-)-PIA). There was no marked difference between the three fat deposits in terms of maximal binding for both radioligands. Saturation and competition experiments showed that the proportion of receptors in the high-affinity state for the agonists was very high (70-91%), but only 33-44% of them were guanine nucleotide-sensitive. Moreover the guanine nucleotides were shown to enhance the specific binding of the antagonist [H-3]DPCPX by decreasing its K(D) value. These binding properties are strongly different from those of another G(i)-coupled receptor on the human fat cell, the alpha-2A-adrenoceptor, and indicates that the adenosine A1 receptor and the alpha-2-adrenoceptor could be differentially coupled with G(i) proteins in the human fat cell.