title: Nitrergic neuro-muscular transmission is up-regulated in patients with diverticulosis.
abstract: BACKGROUND
  Neuro-transmission impairment could be associated to motility changes observed in patients with diverticular disease. Therefore, the objective was to characterize the inhibitory neuro-muscular transmission and gene expression changes of the enteric inhibitory pathways in patients with diverticulosis (DS).
  
  
  METHODS
  Circular muscle strips from sigmoid colon of patients with DS and controls were studied using the organ bath technique to evaluate spontaneous contractility and enteric motor neurons stimulated by electrical field and qRT-PCR to assess the expression of nNOS, iNOS, P2Y1 R and PGP9.5.
  
  
  RESULTS
  Patients with DS presented decreased spontaneous rhythmic contractions (SRC) that were significantly enhanced after incubation with L-NNA (1 mM) and TTX (1 μM), and unaffected by the P2Y1 antagonist MRS2500 (1 μM). Stimulation on enteric motor neurons caused an increased duration of the latency of OFF-contractions in DS group (p < 0.001), antagonized by L-NNA and slightly affected by MRS2500 (1 μM). No differences in the IC50 between controls and DS patients were observed on inhibition of SRC for the NO-donor sodium nitroprusside (SNP) and the preferential P2Y agonist ADPβS. Moreover, nNOS relative expression was also up-regulated 2.3-fold in the DS group (p < 0.05) whereas there was no significant difference in relative expression of iNOS, P2Y1 R and the neuronal marker PGP9.5 between groups.
  
  
  CONCLUSIONS
  Patients with DS presented an over-expression of nNOS with increased endogenously NO-mediated responses suggesting enhanced NO-release. Up-regulation in the nitrergic pathway in early stages of the disease might play a role in colonic motor disorders associated to diverticular disease.
authors.affiliation: Department of Surgery, Gastrointestinal Physiology Laboratory, Hospital de Mataró, Mataró, Barcelona, Spain.
authors.forename: F
authors.initials: F
authors.lastname: Espín
authors.forename: L
authors.initials: L
authors.lastname: Rofes
authors.forename: O
authors.initials: O
authors.lastname: Ortega
authors.forename: P
authors.initials: P
authors.lastname: Clavé
authors.forename: D
authors.initials: D
authors.lastname: Gallego
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D043963:Diverticulosis, Colonic / Q000201:enzymology* / Q000503:physiopathology*; D017615:Enteric Nervous System / Q000503:physiopathology; D005260:Female; D015870:Gene Expression; D006801:Humans; D008297:Male; D008875:Middle Aged; D009046:Motor Neurons / Q000502:physiology; D009130:Muscle, Smooth / Q000201:enzymology / Q000503:physiopathology; D052248:Nitric Oxide Synthase Type I / Q000235:genetics*; D052247:Nitric Oxide Synthase Type II / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D058472:Receptors, Purinergic P2Y1 / Q000235:genetics; D015398:Signal Transduction; D009435:Synaptic Transmission; D043222:Ubiquitin Thiolesterase / Q000235:genetics; D015854:Up-Regulation
chemical_list: D012333:RNA, Messenger; D058472:Receptors, Purinergic P2Y1; C482860:UCHL1 protein, human; C496319:NOS2 protein, human; D052248:Nitric Oxide Synthase Type I; D052247:Nitric Oxide Synthase Type II; D043222:Ubiquitin Thiolesterase
keywords: diverticular disease; motility; nNOS; nitric oxide