ß1-Adrenergic receptor downregulates the expression of cyclooxygenase-2.

Cyclooxygenase-2 (COX-2) catalyzes the rate-limiting step in the generation of prostanoids, and is thus one of the key players in the inflammatory process. Contrary to the constitutively expressed isoform COX-1, the expression of COX-2 is rapidly and transiently upregulated following pathological stimuli but little is known about pathways that mediate its degradation. Here we show that co-expression of COX-2 together with the ß1 adrenergic receptor (ß1AR) specifically lowers the expression of COX-2 in a dose-dependent manner. We further find that stimulation of the receptor for prolonged periods of time does not reverse the ß1AR-induced decrease in COX-2, suggesting that this effect does not occur via classical ß1-mediated signaling pathways. Rather we find that the half-life of COX-2 is significantly decreased in the presence of ß1AR and that inhibition of the proteasome reverses the effect of the receptor on COX-2. Together these findings ascribe a new role for ß1AR in the downregulation of COX-2.