title: Role of M2 and M3 muscarinic acetylcholine receptor subtypes in activation of bladder afferent pathways in spinal cord injured rats.
abstract: OBJECTIVE
  To evaluate the role of M2 and M3 muscarinic acetylcholine receptor (mAChR) subtypes in the activation of bladder afferent pathways in rats with chronic spinal cord injury (SCI).
  
  
  METHODS
  Adult female Sprague-Dawley rats were spinalized at the T9 level. Continuous cystometry was performed under awake conditions 2 or 4 weeks after SCI. The effects of intravesical administration of an mAChR agonist (oxotremorine-methiodide), a nonselective antagonist (atropine), an M2-selective antagonist (methoctramine), and an M3-selective antagonist (darifenacin) were examined. After cystometry, the bladder was removed and separated into the mucosa and detrusor, and the M2 and M3 mAChR mRNA expression in the mucosa was determined using real-time quantitative polymerase chain reaction.
  
  
  RESULTS
  At 2 and 4 weeks after SCI, intravesical administration of a nonselective mAChR agonist (25 μM oxotremorine-methiodide) increased the area under the curve of nonvoiding contractions, although the intercontraction interval of voiding contractions and maximal voiding pressure did not change. This effect was blocked by atropine and methoctramine (10 μM) but not by darifenacin (50 μM). However, mAChR antagonists alone (10-50 μM) had no effect on cystometric parameters. M2 mAChR mRNA expression was increased in the mucosa of SCI rats compared with that in normal rats.
  
  
  CONCLUSIONS
  Our results suggest that the M2 mAChR subtype plays an important role in bladder afferent activation that enhances detrusor overactivity in SCI rats. However, because mAChR antagonists alone did not affect any cystometric parameters, the muscarinic mechanism controlling bladder afferent activity might not be involved in the emergence of detrusor overactivity in SCI.
authors.affiliation: Department of Urology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15213, USA.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Matsumoto
authors.forename: Minoru
authors.initials: M
authors.lastname: Miyazato
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Yokoyama
authors.forename: Masafumi
authors.initials: M
authors.lastname: Kita
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Hirao
authors.forename: Michael B
authors.initials: MB
authors.lastname: Chancellor
authors.forename: Naoki
authors.initials: N
authors.lastname: Yoshimura
mesh_terms: D000344:Afferent Pathways / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D001572:Benzofurans / Q000494:pharmacology; D003959:Diamines / Q000494:pharmacology; D005260:Female; D009092:Mucous Membrane / Q000378:metabolism; D018721:Muscarinic Agonists / Q000494:pharmacology; D018727:Muscarinic Antagonists / Q000494:pharmacology*; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects; D010095:Oxotremorine / Q000031:analogs & derivatives / Q000494:pharmacology; D010276:Parasympatholytics / Q000494:pharmacology; D011312:Pressure; D011759:Pyrrolidines / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D043585:Receptor, Muscarinic M2 / Q000378:metabolism*; D043587:Receptor, Muscarinic M3 / Q000378:metabolism*; D013119:Spinal Cord Injuries / Q000150:complications / Q000503:physiopathology; D013904:Thoracic Vertebrae; D001743:Urinary Bladder / Q000294:innervation / Q000378:metabolism* / Q000503:physiopathology; D053201:Urinary Bladder, Overactive / Q000209:etiology / Q000378:metabolism* / Q000503:physiopathology
chemical_list: D001572:Benzofurans; D003959:Diamines; D018721:Muscarinic Agonists; D018727:Muscarinic Antagonists; D010276:Parasympatholytics; D011759:Pyrrolidines; D012333:RNA, Messenger; D043585:Receptor, Muscarinic M2; D043587:Receptor, Muscarinic M3; D010095:Oxotremorine; D001285:Atropine; C101207:darifenacin; C054938:methoctramine