Evidence that epinephrine acts preferentially as an antilipolytic agent in abdominal human subcutaneous fat cells: assessment by analysis of beta and alpha2 adrenoceptors properties

Abstract

Investigations were carried out to demonstrate the function and the possible advantage of the interplay between β₁ and α₂ adrenoceptor sites in the regulation of human subcutaneous fat-cell lipolysis. α₂ and β adrenoceptor binding studies were conducted with antagonist radioligands and revealed that α₂-adrenoceptors ([³H] yohimbine and [³H] rauwolscine binding sites) are more numerous than β₁-adrenoceptors ([³H] dihydroalprenolol and [³H]CGP-12177 binding sites) in human fat-cell membranes. Physiological agonists epinephrine and norepinephrine competed with [³H]-ligand sites with a higher affinity for α₂ sites than for β₁ sites. Epinephrine exhibited a higher affinity than norepinephrine for the α₂ sites; the two amines had the same affinity for β₁ sites. In lipolysis studies conducted in the absence of adenosine deaminase the β lipolytic action of the biological amines predominated; after α₂-adrenoceptor blockade by yohimbine or idazoxan, the amines exhibited an intrinsic activity similar to that of isoproterenol. When adenosine was prevented from accumulating in the incubation medium by inclusion of adenosine deaminase, low concentrations of epinephrine and norepinephrine preferentially exerted an antilipolytic action. We conclude that: (i) the lipolytic response in abdominal human subcutaneous fat cells to physiological amines results from the interplay between β₁- and α₂-adrenoceptor stimulation; (ii) α₂- adrenoceptors, with their higher number and higher affinity for the physiological amines, and the adrenoceptor population involved at the lowest (i.e. physiological) concentrations of the amines; and (iii) the β₁ sites with a lower number and weaker affinity for epinephrine and norepinephrine are involved when higher concentrations of the amines reach the plasma membrane. Thus, α₂ adrenoceptors appear to be hormonal extrasynaptic receptors which control the state of activity of the human fat cell.