Premium
Nitrergic and purinergic mechanisms evoke inhibitory neuromuscular transmission in the human small intestine
Author(s) -
Gallego D.,
Malagelada C.,
Accarino A.,
De Giorgio R.,
Malagelada J. R.,
Azpiroz F.,
Jimenez M.
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.12293
Subject(s) - purinergic receptor , neurotransmission , inhibitory postsynaptic potential , neuromuscular transmission , ileum , medicine , endocrinology , chemistry , interstitial cell of cajal , jejunum , agonist , receptor , ppads , p2y receptor , neurotransmitter , biology , smooth muscle
Abstract Background Inhibitory neuromuscular transmission in the human colon is due to nitrergic and purinergic (P2Y 1 ‐mediated) inputs. The aim of this study was to determine the mechanisms of neuromuscular transmission in different regions of the human small intestine. Methods Ileal (n = 6) and jejunal (n = 6) samples underwent histological examination and were studied using sharp microelectrodes in smooth muscle cells and conventional muscle bath techniques. Electrical field stimulation ( EFS ) was used to stimulate inhibitory neurons. Key Results No histological abnormalities were found. Resting membrane potential was −39.7 ± 1.5 and −45.5 ± 2.1 mV in the jejunum and ileum, respectively. Slow waves and spontaneous contractions were recorded at a frequency of about 8–9 and 6–7 cpm in the jejunum and ileum, respectively. In non‐adrenergic, non‐cholinergic conditions, EFS caused an inhibitory junction potential and mechanical relaxation. Both responses were blocked by tissue incubation with the nitric oxide synthase inhibitor (Nω‐nitro‐ l ‐arginine 1 mM) and the P2Y 1 receptor blocker 2′‐deoxy‐N 6 ‐methyladenosine 3′,5′‐bisphosphate tetrasodium salt ( MRS 2179; 10 μM). Both exogenous addition of sodium nitroprusside (1 μM) and the preferential P2Y 1 receptor agonist ADP βS (1 μM) hyperpolarized and relaxed smooth muscle cells. MRS 2179 (10 μM) blocked ADP βS‐induced responses. Conclusions & Inferences Similar to colon, inhibitory neurotransmission in the human small intestine is mainly mediated by purinergic (via P2Y 1 receptors) and nitrergic inhibitory neurotransmission. Similar mechanisms of inhibitory neurotransmission are present in different regions of the human intestine.