I stumbled across this searching for AR agonists, but it seams promising.
-ADRENERGIC RECEPTOR POPULATION IS UP-REGULATED IN CHICKEN SKELETAL MUSCLE CELLS TREATED WITH FORSKOLIN. K.Y. Bridge, R.B. Young, and J.R. Vaughn. Marshall Space Flight Center, ES76, Huntsville, AL.
Skeletal muscle hypertrophy is promoted by in vivo administration of -adrenergic receptor ( AR) agonists. These compounds presumably exert their physiological action through the AR, and alterations in the population of AR could potentially change the ability of the cell to respond to the AR agonists. Since the intracellular chemical signal generated by the AR is cyclic AMP (cAMP), experiments were initiated in primary chicken muscle cell cultures to determine if artificial elevation of intracellular cAMP by treatment with forskolin would alter the population of functional AR expressed on the surface of muscle cells. Chicken skeletal muscle cells after 7 days in culture were employed for the experiments because muscle cells have attained a steady state with respect to muscle protein metabolism at this stage. Cells were treated with 0-10 µM forskolin for a total of three days. At the end of the 1, 2, and 3 day treatment intervals, the concentration of cAMP and the AR population were measured. Receptor population was measured in intact muscle cell cultures as the difference between total binding of [3H]CGP-12177 and non-specific binding of [3H]CGP-12177 in the presence of 1 µM propranolol. Intracellular cAMP concentration was measured by radioimmunoassay. The concentration of cAMP in forskolin-treated cells increased up to 10-fold in a dose dependent manner. Increasing concentrations of forskolin also led to an increase in AR population, with a maximum increase of approximately 50% at 10 µM. This increase in AR population was apparent after only 1 day of treatment, and the pattern of increase was maintained for all 3 days of the treatment period. Thus, increasing the intracellular concentration of cAMP leads to up-regulation of AR population. The effect of forskolin on the quantity and apparent synthesis rate of the heavy chain of myosin (mhc) were also investigated. A maximum increase of 50% in the quantity of mhc was observed at 0.2 µM forskolin, but higher concentrations of forskolin reduced the quantity of mhc back to control levels.