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Specific and complementary roles for nitric oxide and ATP in the inhibitory motor pathways to rat internal anal sphincter
Author(s) -
Opazo A.,
Lecea B.,
Gil V.,
Jiménez M.,
Clavé P.,
Gallego D.
Publication year - 2011
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/j.1365-2982.2010.01602.x
Subject(s) - vasoactive intestinal peptide , internal anal sphincter , inhibitory postsynaptic potential , stimulation , nitric oxide , medicine , endocrinology , chemistry , receptor , purinergic receptor , biology , neuropeptide , anal canal , rectum
Background The neurotransmitters mediating inhibitory pathways to internal anal sphincter (IAS) have not been fully characterized. Our aim was to assess the putative release of nitric oxide, purines and vasoactive intestinal peptide (VIP) from inhibitory motor neurons (MNs) and their role in the myogenic tone, resting membrane potential (RMP) of smooth muscle cells (SMC), spontaneous inhibitory junction potentials (sIJP), mechanical relaxation, and IJP induced by electrical field stimulation (EFS) or nicotine. Methods Rat IAS strips were studied using organ baths, microelectrodes, and immunohistochemistry. Key Results Internal anal sphincter strips developed active myogenic tone (0.31 g), enhanced and stabilized by prostaglandin F 2α (PGF2α). l ‐ NNA (1 mmol L −1 ) depolarized SMC and increased tone but did not modify sIJP. In contrast, the specific P2Y 1 receptor antagonist MRS2500 (1 μ mol L −1 ) did not modify the RMP or the basal tone but abolished sIJP. Electrical field stimulation and nicotine (10 μ mol L −1 ) caused IAS relaxation (−45.9% VS −52.2%), partially antagonized by l ‐ NNA (35%–45%, P ≤ 0.05) and fully abolished by MRS2500 ( P ≤ 0.001). Electrical field stimulation induced a biphasic inhibitory junction potential (IJP), the initial fast component was selectively blocked by MRS2500 and the sustained slow component was blocked by l ‐ NNA. Vasoactive intestinal peptide 6–28 (0.1 μ mol L −1 ) or α‐chymotrypsin (10 U mL −1 ) did not modify the RMP, sIJP, EFS‐induced IJP, or relaxation. P2Y 1 receptors were immunolocalized in the circular SMC of IAS. Conclusions & Inferences The effects of inhibitory MNs on rat IAS are mediated by a functional co‐transmission process involving nitrergic and purinergic pathways through P2Y 1 receptors with specific and complementary roles on the control of tone, sIJP, and hyperpolarization and relaxation of IAS following stimulation of inhibitory MNs.