β‐Adrenergic receptor trafficking by exercise in rat adipocytes: roles of G‐protein‐coupled receptor kinase‐2, β‐arrestin‐2, and the ubiquitin‐proteasome pathway

• Published in: The FASEB journal 2006-02, Vol.20 (2), p.350-352
• Main Authors: Ogasawara, Junetsu, Sanpei, Minori, Rahman, Nazibur, Sakurai, Tomonobu, Kizaki, Takako, Hitomi, Yoshiaki, Ohno, Hideki, Izawa, Tetsuya
• Format: Article
• Language: English
• Subjects: Adipocytes - metabolism; Animals; Arrestins - genetics; Arrestins - metabolism; beta-Adrenergic Receptor Kinases - genetics; beta-Adrenergic Receptor Kinases - metabolism; beta-Arrestin 2; beta-Arrestins; Cyclic AMP - metabolism; down‐regulation; G-Protein-Coupled Receptor Kinase 2; Gene Expression Regulation; lactacystin; Male; Physical Conditioning, Animal - physiology; Proteasome Endopeptidase Complex - metabolism; Rats; Rats, Wistar; Receptors, Adrenergic, beta - genetics; Receptors, Adrenergic, beta - metabolism; RNA, Messenger - metabolism; Ubiquitin - metabolism; ubiquitination
• ISSN: 0892-6638; 1530-6860
• DOI: 10.1096/fj.05-4688fje

ABSTRACT The effect of exercise on β‐adrenergic receptor (β‐AR) trafficking was investigated in rat adipocytes. The binding sites of a hydrophilic ligand, [3H]CGP12177, increased immediately (0 h) and at 3 h after exercise (3 h) but decreased at 24 h after exercise (24 h). The data of immunoblotting revealed that the alterations in the binding sites mainly paralleled the alterations in the β2‐AR proteins in membrane fractions. The protein expressions of both G‐protein‐coupled receptor kinase (GRK)‐2 and β‐arrestin‐2 were reduced, with a decline in β2‐AR ubiquitination at 0 h and 3 h. The protein expressions of β2‐AR, GRK‐2, β‐arrestin‐2, the β2‐AR/β‐arrestin‐2 complex, and β2‐AR ubiquitination returned to their respective control levels at 24 h, whereas the β2‐AR mRNA level was reduced. Administration of either lactacystin or propranolol did not alter GRK‐2 and β2‐AR protein expressions after exercise. Thus, the mechanism underlying the increased density of β2‐AR up to at least 3 h may involve alterations in a multistep event involving the coordinate interaction among proteins mediating β2‐AR trafficking, in which both the receptor‐agonist interactions and ubiquitin‐proteasome pathway have a key role. However, the decreased protein expression of β2‐AR at 24 h might be due to some change occurring at the translational levels.