The inhibitory role of acetylcholine and muscarinic receptors in bladder afferent activity.
BACKGROUND
The main treatment for overactive bladder (OAB) is the use of anticholinergic drugs initially believed to inhibit the effect of parasympathetic acetylcholine (ACh) on the detrusor; however, there is now evidence to suggest that anticholinergic drugs could interact with sensory pathways.


OBJECTIVE
Investigate the role of muscarinic receptors and ACh in modulating bladder afferent sensitivity in the mouse.


METHODS
Bladder and surrounding tissue were removed from wild-type male mice, placed in a recording chamber, and continually perfused with fresh oxygenated Krebs solution at 35 degrees C. Bladders were cannulated to allow infusion and intravesical pressure monitoring, and afferent nerve fibres innervating the bladder were dissected and put into a suction electrode for recording.


METHODS
Multiunit afferent activity and intravesical pressure were recorded at baseline and during bladder distension. Experiments were conducted in the presence of muscarinic agonists and antagonist or in the presence of the cholinesterase inhibitor physostigmine.


CONCLUSIONS
Blocking muscarinic receptors using atropine (1 microM) had no effect on spontaneous afferent discharge, the afferent response to bladder distension, or on bladder compliance. However, stimulation of muscarinic receptors directly using bethanechol (100 microM) and carbachol (100 microM) or indirectly using physostigmine (10 microM) significantly inhibited the afferent response to bladder distension and concurrently reduced bladder compliance. Furthermore, prior application of nifedipine prevented the changes in bladder tone but did not prevent the attenuation of afferent responses by bethanechol or physostigmine.


CONCLUSIONS
These data indicate that stimulation of muscarinic receptor pathways can depress sensory transduction by a mechanism independent of changes in bladder tone, suggesting that muscarinic receptor pathways and ACh could contribute to normal or pathologic bladder sensation.
Daly
Donna M
DM
University of Sheffield, Western Bank, Sheffield, UK. dalyd@queensu.ca
Chess-Williams
Russell
R
Chapple
Christopher
C
Grundy
David
D
D000109:Acetylcholine / Q000502:physiology; D000818:Animals; D002800:Cholinesterase Inhibitors / Q000494:pharmacology; D008297:Male; D051379:Mice; D018721:Muscarinic Agonists / Q000494:pharmacology; D018727:Muscarinic Antagonists / Q000494:pharmacology; D009475:Neurons, Afferent / Q000187:drug effects / Q000502:physiology*; D010830:Physostigmine / Q000494:pharmacology; D011976:Receptors, Muscarinic / Q000502:physiology*; D001743:Urinary Bladder / Q000187:drug effects / Q000294:innervation / Q000502:physiology*
D002800:Cholinesterase Inhibitors; D018721:Muscarinic Agonists; D018727:Muscarinic Antagonists; D011976:Receptors, Muscarinic; D010830:Physostigmine; D000109:Acetylcholine