The effects of acute exercise on the protein expressions of heterotrimeric G protein alpha subunits were examined in rat adipocytes. Galphai2 protein expression was significantly reduced 0 and 3 h after exercise but increased 24 h after exercise, without alterations in Galphai2 mRNA expressions. The protein expressions of other alpha subunits, Galphas, Galphai1, and Galphai3, were not influenced. Both the 26S proteasome activity and polyubiquitination of Galphai2 protein were significantly increased 0 and 3 h after exercise. Whereas, proteasome activity was decreased, and the polyubiquitination of Gai2 protein was returned to the control level 24 h after exercise. The reductions in Gai2 protein expressions 0 and 3 h after exercise were completely prevented by the injection either of a proteasome inhibitor or of a beta-adrenergic receptor blocker prior to exercise. Thus, acute exercise altered the expression of Galphai2 protein via mechanisms which involve the coupling of beta-adrenergic receptors to an agonist with subsequent ubiquitin-proteasome-dependent proteolysis. (C) 2004 Elsevier Inc. All rights reserved.