ORCID Profile
0000-0003-2578-9565
Current Organisation
Universidad Andres Bello
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Publisher: Wiley
Date: 10-11-2009
DOI: 10.1111/J.1365-2982.2009.01357.X
Abstract: The mechanisms of stimulation of inhibitory and excitatory motor neurons (MNs) in the lower oesophageal sphincter (LOS) are not fully understood. The aim of this study was to assess the effect of selective stimulation of inhibitory and excitatory MNs in porcine LOS through nicotinic acetylcholine receptors (nAChRs), 5-HT(3) and P2X receptors. Circular LOS strips from adult pigs were studied in organ baths. We compared the effects of stimulation of MNs by electrical field stimulation (26 V, 0.3-20 Hz) nicotine (1-300 micromol L(-1)) 5-HT and 2-Me-5-HT (1 nmol(-1)-30 micromol L(-1)) and alpha,beta-methylene ATP (alpha,beta-meATP 1-100 micromol L(-1)) in standard Krebs solution a non-adrenergic non-nitrergic non-purinergic (NANNNP) solution and a non-adrenergic non-cholinergic (NANC) solution. Electrical stimulation of inhibitory MNs caused an intense LOS relaxation (-78.94 +/- 4.50% of LOS tone) and of excitatory MNs, a strong contraction (17.89 +/- 1.96 g). Nicotine 100 micromol L(-1) relaxed LOS (-84.67 +/- 3.98%) in standard Krebs solution, an effect reduced by Tetrodotoxin (TTX) 1 micromol L(-1). Nicotine induced a weak TTX-sensitive contraction (1.64 +/- 0.4 g) in NANNNP solution. 5-HT 10 micromol L(-1) and 2-Me-5-HT 30 micromol L(-1) contracted LOS in standard, NANC and NANNNP conditions, maximal responses (7.30 +/- 1.52 g, 3.50 +/- 0.18 g respectively) being reduced by TTX. alpha,beta-meATP 100 micromol L(-1) caused a LOS relaxation (-17.45 +/- 6.62%) unaffected by TTX in NANC solution, and a contraction (6.7 +/- 0.85 g) antagonized by TTX in NANNNP solution. Our results suggest selective mechanisms for stimulation of intrinsic excitatory and inhibitory motor pathways in porcine LOS. Inhibitory MNs are strongly stimulated by nAChRs and do not respond to stimulation of 5-HT(3) and P2X receptors. By contrast, excitatory MNs are stimulated through 5-HT(3) and P2X receptors, stimulation through nACRs being difficult and causing a weak response.
Publisher: American Physiological Society
Date: 05-2011
Abstract: The aim of this study was to explore the myenteric mechanisms of control of human esophageal motility and the effect of nitrergic and nonnitrergic neurotransmitters. Human circular esophageal strips were studied in organ baths and with microelectrodes. Responses following electrical field stimulation (EFS) of enteric motoneurons (EMNs) or through nicotinic acetylcholine receptors were compared in the esophageal body (EB) and in clasp and sling regions in the lower esophageal sphincter (LES). In clasp LES strips: 1) sodium nitroprusside (1 nM to 100 μM), adenosine-5′-[β-thio]diphosphate trilithium salt (1–100 μM), and vasoactive intestinal peptide (1 nM to 1 μM) caused a relaxation 2) 1 mM N ω -nitro-l-arginine (l-NNA) shifted the EFS “on”-relaxation to an “off”-relaxation, partly antagonized by 10 μM 2′-deoxy- N 6 -methyladenosine 3′,5′-bisphosphate tetrasodium salt (MRS2179) or 10 U/ml α-chymotrypsin and 3) nicotine-relaxation (100 μM) was mainly antagonized by l-NNA, and only partly by MRS2179 or α-chymotrypsin. In sling LES fibers, EFS and nicotine relaxation was abolished by l-NNA. In the EB, l-NNA blocked the latency period, and MRS2179 reduced “off”-contraction. The litude of cholinergic contraction decreased from the EB to both LES sides. EFS induced a monophasic inhibitory junction potential in clasp, sling, and EB fibers abolished by l-NNA. Our study shows a regional specialization to stimulation of EMNs in the human esophagus, with stronger inhibitory responses in clasp LES fibers and stronger cholinergic excitatory responses in the EB. Inhibitory responses are mainly triggered by nitrergic EMNs mediating the inhibitory junction potentials in the LES and EB, EFS on-relaxation in clasp and sling LES sides, and latency in the EB. We also found a minor role for purines (through P2Y 1 receptors) and vasoactive intestinal peptide-mediating part of nonnitrergic clasp LES relaxation.
Publisher: Wiley
Date: 03-10-2010
DOI: 10.1111/J.1365-2982.2010.01602.X
Abstract: 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. Rat IAS strips were studied using organ baths, microelectrodes, and immunohistochemistry. 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 μmol L(-1)) did not modify the RMP or the basal tone but abolished sIJP. Electrical field stimulation and nicotine (10 μmol 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 μmol 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. 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.
Publisher: Wiley
Date: 12-2008
DOI: 10.1038/BJP.2008.332
Publisher: Wiley
Date: 27-03-2013
DOI: 10.1111/CODI.12095
Abstract: The patterns of impaired internal anal sphincter activity were studied in patients with anal fissure (AF). Twenty healthy controls and 61 patients with acute AF were studied, using anorectal manometry with electromyography (EMG), and 53 patients with chronic AF using high-resolution manometry and ultrasonography. Mean and maximal resting anal pressure (MRAP), spontaneous rhythmic slow and ultraslow waves (USW) and relaxation induced by rectal distension were measured. Patients with acute AF had higher mean (106.4 ± 28.1 mmHg) and maximal resting anal pressure (161.5 ± 43.7 mmHg) than those with chronic AF (P < 0.05) 95% of patients had slow waves (SW) and 67% ultraslow waves. Patients with chronic AF had higher mean (92.4 ± 22.6 mmHg) and maximal resting anal pressure (117.5 ± 32.0 mmHg) than controls and 94% of patients had slow waves and 69% ultraslow waves. Patients with ultraslow waves (with either acute or chronic AF) had increased internal sphincter hypertonicity (mean and maximal resting pressure), decreased internal sphincter relaxation and increased after-contraction following rectal distension. Patients with acute AF had higher hypertonicity than those with chronic AF and both had increased spontaneous rhythmic activity (waves). Patients with AF and ultraslow waves had higher internal anal sphincter hypertonicity and reduced internal sphincter relaxation and enhanced after-contraction following rectal distension.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 11-2009
No related grants have been discovered for Alvaro Opazo Valdes.