Neuronal pathways and transmission to the lower esophageal sphincter of the guinea pig

Shi, Yuanquan; Costa, Marcello; Brookes, Simon J.

doi:10.1016/s0016-5085(98)70145-3

Cited by 61 publications

(49 citation statements)

References 53 publications

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“…These results in the human LES agree with our laboratory's previous studies on pigs (8) and previous studies in cats (16), which found that stimulation of EMNs induces stronger inhibitory responses in clasp fibers and stronger excitatory responses in sling fibers. Supporting our results on both humans and pigs, studies on the guinea pig LES also show a marked functional neural asymmetry, as vagal stimulation causes activation of excitatory and inhibitory EMNs on the sling LES side (40) and only inhibitory responses in the clasp (39). In addition, all of these functional studies and our present results on humans agree with morphological studies mapping the regional distribution of EMNs in guinea pig LES that found that, in the clasp region, 33% of the neurons stain positively for cholineacetyl-transferase, whereas 70% stain positively for NO synthase (2).…”

Section: Discussionsupporting

confidence: 87%

Regional functional specialization and inhibitory nitrergic and nonnitrergic coneurotransmission in the human esophagus

Lecea

Gallego

Farré

et al. 2011

American Journal of Physiology-Gastrointestinal and Liver Physi

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Lecea B, Gallego D, Farré R, Opazo A, Aulí M, Jiménez M, Clavé P. Regional functional specialization and inhibitory nitrergic and nonnitrergic coneurotransmission in the human esophagus. Am J Physiol Gastrointest Liver Physiol 300: G782-G794, 2011. First published February 17, 2011 doi:10.1152/ajpgi.00514.2009.-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 M), adenosine-5=-[␤-thio]diphosphate trilithium salt (1-100 M), and vasoactive intestinal peptide (1 nM to 1 M) caused a relaxation; 2) 1 mM N -nitro-L-arginine (L-NNA) shifted the EFS "on"-relaxation to an "off"-relaxation, partly antagonized by 10 M 2=-deoxy-N 6 -methyladenosine 3=,5=-bisphosphate tetrasodium salt (MRS2179) or 10 U/ml ␣-chymotrypsin; and 3) nicotine-relaxation (100 M) was mainly antagonized by L-NNA, and only partly by MRS2179 or ␣-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 amplitude 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 P2Y1 receptors) and vasoactive intestinal peptide-mediating part of nonnitrergic clasp LES relaxation. lower esophageal sphincter; esophageal body; inhibitory motoneurons; inhibitory coneurotransmission THE MAIN PHYSIOLOGICAL FUNCTION of the lower esophageal sphincter (LES) is to generate a zone of high pressure that prevents the reflux of acid gastric content into the esophagus. LES relaxations occur briefly after swallowing, and transient LES relaxations cause physiological gastroesophageal reflux and allow belching. Enteric motoneurons (EMNs) are the final step in the inhibitory vagal pathway to the LES, mediating swallow-induced and transient LES relaxation (3). Nitric oxide (NO) released from these inhibitory EMNs is the major contributor to LES relaxation in humans (12) and opossums (20, 33). However, vasoactive intestinal peptide (VIP) and ATP are putative inhibitory neurotransmitters in animal studies (14, 21-24, 34, ...

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Section: Discussionsupporting

confidence: 87%

Regional functional specialization and inhibitory nitrergic and nonnitrergic coneurotransmission in the human esophagus

Lecea

Gallego

Farré

et al. 2011

American Journal of Physiology-Gastrointestinal and Liver Physi

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“…In various species, stimulation of intrinsic enteric nerves evokes NANC IJPs in LOS (Conklin et al, 1993;Yuan et al, 1998;Ward et al, 1999). The considerable neurotransmitters involve NO, ATP, vasoactive intestinal polypeptide and pituitary adenylate cyclase-activating polypeptide, and responsible channels suggested are apamin-sensitive K + channels and apamininsensitive channels (Rae and Muir, 1996;Imaeda et al, 1998;Selemidis et al, 1998).…”

Section: Discussionmentioning

confidence: 99%

“…It is also the case in the LOS of several species. NO has been clarified as the important transmitter of IJP in opossum (Conklin et al, 1993), dog (De Man et al, 1991), cat (Ny et al, 1995) and guinea-pig (Imaeda et al, 1998, Yuan et al, 1998. So, NO is a potential candidate for the neurotransmitter of IJP in the murine LOS.…”

Section: Nitrergic Fast and Slow Ijpsmentioning

confidence: 99%

“…Clarification of the underlying mechanisms of the generation of IJP leads to the identification not only of the transmitter(s) but also of the channel(s) involved in these hyperpolarising responses. IJP in LOS are observed in several experimental animals, for example dog (Allescher et al, 1988), opossum (Daniel et al, 1989;Conklin et al, 1993), guineapig (Imaeda et al, 1998;Yuan et al, 1998) and mouse (Ward et al, 1998). In the guinea-pig LOS, nitric oxide (NO) and adenosine triphospahte (ATP) have been proposed as inhibitory neurotransmitters and small conductance Ca 2+ -activated K + (SKCa) channels played an important role in eliciting IJP (Imaeda et al, 1998).…”

Section: Introductionmentioning

confidence: 99%

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Electrophysiological Properties of Inhibitory Junction Potential in Murine Lower Oesophageal Sphincter.

Imaeda

Cunnane

2003

J. Smooth Muscle Res.

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The electrophysiological properties of smooth muscle in the murine lower oesophageal sphincter (LOS) were investigated by intracellular microelectrode recording. Inhibitory junction potentials (IJPs) evoked by trains of field stimulation (30 V, 0.2-0.3 ms, 10 stimuli at 1-50 Hz) were observed in the murine LOS in the presence of atropine (1 µM) and nifedipine (1 µM). The IJP consists of two components, which we termed fast IJP and slow IJP. The fast IJP was partly sensitive to guanethidine (5 µM), pyridoxalphosphate-6-azophenyl-2',4'-disulphonic acid (PPADS, 30 µM) and apamin (0.1 µM), suggesting that the fast IJP was produced partly through the activation of apamin- and charybdotoxin (30 nM). KT5823, a protein kinase G (PKG) inhibitor, had no effect on the fast and slow IJP in this tissue. It was suggested that, in the mouse LOS, adenosine trisphosphate (ATP) partly mediated the fast IJP through apamin-sensitive Ca 2+ -activated K + channels, and nitric oxide mediated the remained part of the fast IJP and the slow IJP through cGMP, but not PKG. ATP-sensitive K + channels were suggested to be partly involved in the production of slow IJP, but the responsible channel(s) for the nitrergic fast IJP remained unclarified.

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“…There is evidence for the involvement of ATP in the control of pyloric and internal anal sphincters [562,629] and in the NANC inhibitory responses of the lower oesophageal sphincter [351,743]. Studies of NANC inhibitory responses of the rat pyloric sphincter provided evidence for components mediated by both NO and ATP [354,629] via P2Y 1 receptors, but P2X4 receptors were also expressed in this sphincter [596].…”

Section: Sphincter Controlmentioning

confidence: 99%

Purinergic signalling in the gastrointestinal tract and related organs in health and disease

Burnstock

2013

Purinergic Signalling

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Purinergic signalling plays major roles in the physiology and pathophysiology of digestive organs. Adenosine 5′-triphosphate (ATP), together with nitric oxide and vasoactive intestinal peptide, is a cotransmitter in nonadrenergic, non-cholinergic inhibitory neuromuscular transmission. P2X and P2Y receptors are widely expressed in myenteric and submucous enteric plexuses and participate in sympathetic transmission and neuromodulation involved in enteric reflex activities, as well as influencing gastric and intestinal epithelial secretion and vascular activities. Involvement of purinergic signalling has been identified in a variety of diseases, including inflammatory bowel disease, ischaemia, diabetes and cancer. Purinergic mechanosensory transduction forms the basis of enteric nociception, where ATP released from mucosal epithelial cells by distension activates nociceptive subepithelial primary afferent sensory fibres expressing P2X3 receptors to send messages to the pain centres in the central nervous system via interneurons in the spinal cord. Purinergic signalling is also involved in salivary gland and bile duct secretion.

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Neuronal pathways and transmission to the lower esophageal sphincter of the guinea pig

Cited by 61 publications

References 53 publications

Regional functional specialization and inhibitory nitrergic and nonnitrergic coneurotransmission in the human esophagus

Regional functional specialization and inhibitory nitrergic and nonnitrergic coneurotransmission in the human esophagus

Electrophysiological Properties of Inhibitory Junction Potential in Murine Lower Oesophageal Sphincter.

Purinergic signalling in the gastrointestinal tract and related organs in health and disease

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