Effect of Chronic Atropine Administration on the Rat Urinary Bladder

Abstract

Micturition is accomplished via a coordinated contraction of the urinary bladder body mediated primarily by muscarinic receptor stimulation. Theoretically, bladder function may be modified by pharmacologically altering either the muscarinic receptor density and/or the magnitude of the response to receptor activation. In the central nervous system, autonomic receptor density can be modified by chronic administration of specific receptor agonists and antagonists. The chronic administration of receptor agonists induces a decrease in the specific receptor density whereas the chronic administration of antagonists induces an increase in the specific receptor density. Although these induced alterations in receptor density occur in the CNS, there have been few studies on peripheral tissue.For the current study, we have administered L-atropine chronically to rats (five mg./kg./day) using implanted osmotic pumps. Using direct radioligand binding techniques, the muscarinic receptor density of the rat brain (cortex) and urinary bladder were determined following six hours, 12 hours, one, two, four, seven, 11 and 14 days of atropine administration. In addition, we have also determined the effect of atropine administration on bladder weight and the response of isolated strips of the bladder to bethanechol, a specific muscarinic agonist.For both the brain and the bladder, the receptor density increased progressively and reached a maximum by seven days. At 14 days of atropine administration, the density of muscarinic receptors in rat brain increased significantly (p <.05) from 2956 +/- 74fmoles/mg. protein to 3800 +/- 170fmoles/mg. protein. The muscarinic receptor density of the rat urinary bladder increased significantly from 115 +/- 10fmole/mg. protein to 165+/- 14fmole/mg. protein. Although there was a 42% increase in bladder mass, the contractile response of isolated strips to bethanechol did not change significantly.This study demonstrates that the urinary bladder can respond to the chronic administration of atropine with a significant increase in the density of muscarinic receptors. The magnitude of the increase observed was slightly greater than the magnitude observed for muscarinic receptors isolated from the brain cortex.