Human adipocytes express alpha 2-adrenergic receptor of the alpha 2A-subtype only: pharmacological and genetic evidence.
In the present study we have reinvestigated the subtype of alpha 2-adrenoceptors expressed in human adipocytes (from subcutaneous and internal fat deposits) by means of radioligand binding using subtype-selective antagonists, and RNase mapping using a set of specific probes prepared from human alpha 2-adrenoceptors genes (alpha 2C2, alpha 2C4 and alpha 2C10). Comparison of the pharmacological properties of the human adipocyte alpha 2-adrenoceptors with those of the different human adrenoceptors expressed in COS-7 cells demonstrated that: i) human adipocyte alpha 2-adrenoceptors displays a KD for [3H]RX821002 and [3H]MK912 identical to that found in COS-7 cells transfected with the alpha 2C10 gene; ii) yohimbine and oxymetazoline is 1,000-fold more potent than prazosin to inhibit [3H]antagonist binding. RNase protection assays on cellular RNA prepared from the three fat deposits showed the presence of substantial amounts of alpha 2C10 transcripts: in contrast, mRNAs from alpha 2C2 and alpha 2C4 genes were undetectable. Altogether these results definitively establish that human adipocytes express only one alpha 2-adrenoceptor which is of the alpha 2A-subtype and encoded by the alpha 2C10 gene.
Castan
I
I
Inserm Unité 317, CHU-Rangueil, Toulouse, France.
Devedjian
J C
JC
Valet
P
P
Paris
H
H
Lafontan
M
M
D017667:Adipocytes / Q000378:metabolism*; D000317:Adrenergic alpha-Antagonists / Q000493:pharmacokinetics; D000328:Adult; D002460:Cell Line; D005260:Female; D006801:Humans; D019329:Idazoxan / Q000031:analogs & derivatives / Q000493:pharmacokinetics; D066298:In Vitro Techniques; D008566:Membranes / Q000378:metabolism; D008875:Middle Aged; D011807:Quinolizines / Q000493:pharmacokinetics; D012313:RNA / Q000302:isolation & purification / Q000378:metabolism; D015347:RNA Probes / Q000138:chemical synthesis / Q000494:pharmacology; D011869:Radioligand Assay; D018341:Receptors, Adrenergic, alpha-2 / Q000235:genetics / Q000378:metabolism*; D012260:Ribonucleases / Q000378:metabolism
D000317:Adrenergic alpha-Antagonists; D011807:Quinolizines; D015347:RNA Probes; D018341:Receptors, Adrenergic, alpha-2; C054290:L 657743; D012313:RNA; C058525:2-methoxyidazoxan; D012260:Ribonucleases; D019329:Idazoxan