Effect of contractile activity on muscarinic receptor density and the response to muscarinic agonists.

Autonomic receptor density can be modulated by alterations in neuronal activity over a relatively short period of time (hours). The current study investigates whether increased in vivo stimulation of urinary bladder smooth muscle can alter muscarinic receptor density and response to muscarinic stimulation. A high degree of reflex stimulation of the urinary bladder (rabbits) was initiated by stricture of the external urethra. Intravesical pressure and intra-abdominal pressure were monitored continuously over a 4-hr time period. At the end of the 4-hr period, the rabbits were sacrificed and isolated strips of bladder body were either mounted in isolated smooth muscle baths for contractile studies or frozen and stored in liquid nitrogen for muscarinic receptor analysis. These studies demonstrated that over 4 hr of urethral stricture there was a significant reduction in muscarinic receptor density from a Bmax of 34 +/- 3.4 fmol/mg of protein in control bladder strips to 22 +/- 2.4 fmol/mg of protein in the experimental group. In association with the decreased muscarinic receptor density, there was a significant and selective decrease in the contractile response to muscarinic stimulation. Similar to the in vivo studies, repetitive field stimulation of in vitro strips resulted in a significant decrease in muscarinic receptor density and a significant and selective decrease in the contractile response to muscarinic stimulation. The results from these studies indicate that muscarinic receptor density, and response to muscarinic stimulation, can be modulated over a relatively short period of time by alterations in the level of neuronal stimulation.