Functional effects of long-term activation on @entity1 XXXX - and @entity1093 -adrenoceptor signalling.

@entity1 @entity2162 @entity1093 @entity1919 @entity3044 @entity21276 @entity2263
The functional effects of long-term activation of beta-adrenoceptors were investigated by measuring adenylyl cyclase activity, @entity1919 accumulation and @entity1919 -dependent protein kinase activity in CHW and L cells expressing either @entity1 @entity2263 - or @entity1093 -adrenoceptors. Pre-incubation of CHW and L cells expressing @entity2263 -adrenoceptors with 10 microM @entity3044 for 24 h produced a marked reduction in the total receptor number and dramatically reduced the capacity of the receptor to stimulate adenylyl cyclase maximally. In contrast, the ability of @entity1093 -adrenoceptors number was observed in L but not in CHW cells. Maximal levels of intracellular @entity1919 concentrations were reached during the first hour of receptor activation with @entity3044 in all four cell lines. In the absence of phosphodiesterase inhibitors, @entity1919 decreased to basal levels within 24 h of continuous stimulation. This phenomenon occurred more rapidly in cells expressing the @entity2263 - than the @entity1093 -adrenoceptors. These results confirm that, at the level of adenylyl cyclase stimulation and @entity1919 accumulation, the @entity21276 is more resistant than the @entity2162 to long-term desensitization. However, when @entity1919 -dependent protein kinase activity was considered, a 24 h stimulation of @entity2263 - and when @entity1919 -dependent protein kinase activity was considered, a 24 h stimulation of @entity2263 - and @entity1093 -adrenoceptor expressing cells led to the desensitization of the kinase in L but not in CHW cells. In conclusion, long-term desensitization may have distinct functional effects on cell signalling depending on the receptor subtype and the cell type considered. These findings might have practical implications for future strategies involving long-term therapies with receptor agonists.
