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.