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Nitrergic neuro‐muscular transmission is up‐regulated in patients with diverticulosis
Author(s) -
Espín F.,
Rofes L.,
Ortega O.,
Clavé P.,
Gallego D.
Publication year - 2014
Publication title -
neurogastroenterology and motility
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.489
H-Index - 105
eISSN - 1365-2982
pISSN - 1350-1925
DOI - 10.1111/nmo.12407
Subject(s) - medicine , endocrinology , interstitial cell of cajal , enteric nervous system , stimulation , contractility , agonist , diverticulosis , inhibitory postsynaptic potential , chemistry , sodium nitroprusside , receptor , nitric oxide , smooth muscle
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 q RT ‐ PCR to assess the expression of n NOS , i NOS , P2Y 1 R and PGP 9.5. Key Results Patients with DS presented decreased spontaneous rhythmic contractions ( SRC ) that were significantly enhanced after incubation with L‐ NNA (1 mM) and TTX (1 μ M), and unaffected by the P2Y 1 antagonist MRS 2500 (1 μ M). 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 MRS 2500 (1 μ M). No differences in the IC 50 between controls and DS patients were observed on inhibition of SRC for the NO ‐donor sodium nitroprusside ( SNP ) and the preferential P2Y agonist ADP β S. Moreover, n NOS 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 i NOS , P2Y 1 R and the neuronal marker PGP 9.5 between groups. Conclusions & Inferences Patients with DS presented an over‐expression of n NOS 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.