title: Inhibitory role of the spinal cholinergic system in the control of urethral continence reflex during sneezing in rats.
abstract: OBJECTIVE
  The urethral continence reflex during stress conditions such as sneezing or coughing is an important mechanism preventing stress urinary incontinence (SUI). Although the spinal noradrenergic and serotonergic pathways are known to modulate this reflex activity, the role of spinal cholinergic pathways in the control of urethral continence reflex has not been elucidated. We therefore investigated the effect of intrathecal administration of an acetylcholine esterase (AChE) inhibitor, which increases ACh in synaptic terminals, and anti-cholinergic agents on the sneeze-induced urethral reflex in rats.
  
  
  METHODS
  Female SD rats were anesthetized with urethane. Urethral function was evaluated during sneezing induced by insertion of the rat whisker into the nostril. Effects of an AChE inhibitor, neostigmine, and muscarinic or nicotinic receptor antagonists administered at the level of L6-S1 spinal cord were examined.
  
  
  RESULTS
  Neostigmine dose-dependently and significantly decreased the amplitude of urethral responses during sneezing (A-URS) with an approximately 70% reduction at 3 nmol, without changing urethral baseline pressure. The neostigmine-induced decrease in A-URS was significantly reversed by pretreatment with atropine (nonselective muscarinic receptor antagonist), methoctramine (M2 receptor antagonist) or 4-DAMP (M3 receptor antagonist), but not with pirenzepine (M1 receptor antagonist), tropicamide (M4 receptor antagonist), or mecamylamine (nicotinic receptor antagonist).
  
  
  CONCLUSIONS
  These results indicate that an increase in endogenous ACh in the lumbosacral spinal cord inhibits the sneeze-induced urethral continence reflex via activation of M2 and/or M3-muscarinic receptors, implying the inhibitory role of spinal cholinergic pathways in the control of urethral continence reflex under stress conditions such as sneezing.
authors.affiliation: Department of Urology, University of Pittsburgh, Pittsburgh, Pennsylvania.
authors.forename: Satoru
authors.initials: S
authors.lastname: Yoshikawa
authors.forename: Takeya
authors.initials: T
authors.lastname: Kitta
authors.forename: Minoru
authors.initials: M
authors.lastname: Miyazato
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Sumino
authors.forename: Naoki
authors.initials: N
authors.lastname: Yoshimura
mesh_terms: D000818:Animals; D002800:Cholinesterase Inhibitors / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D005260:Female; D018727:Muscarinic Antagonists / Q000627:therapeutic use; D010275:Parasympathetic Nervous System / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012018:Reflex / Q000187:drug effects / Q000502:physiology*; D012912:Sneezing / Q000187:drug effects / Q000502:physiology*; D013116:Spinal Cord / Q000187:drug effects / Q000502:physiology*; D014521:Urethra / Q000187:drug effects / Q000502:physiology*; D014549:Urinary Incontinence / Q000188:drug therapy / Q000503:physiopathology*
chemical_list: D002800:Cholinesterase Inhibitors; D018727:Muscarinic Antagonists
keywords: acetylcholine; muscarinic receptors; sneeze; spinal cord; stress urinary incontinence; urethral continence reflex