Mechanisms controlling function in the clasp and sling regions of porcine lower oesophageal sphincter

Farré, Ricard; Aulí, Mariona; Lecea, Begoña; Estrada, Óscar; Suñol, Xavier; Clavé, Père

doi:10.1002/bjs.5831

Cited by 21 publications

(40 citation statements)

References 33 publications

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“…In contrast, the direct effect of inhibitory NTs is similar between both LES sides, suggesting this functional asymmetry can be attributed to specialization at the myenteric plexus level. 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).…”

Section: Discussionsupporting

confidence: 92%

“…Full thickness preparations, including the circular and longitudinal muscle layers, as well as the myenteric plexus, were obtained from each LES side (clasp/sling strips) by cutting 3-mm-wide strips parallel to circular muscle fibers (7,12). Up to four consecutive strips were obtained from both the clasp and sling region of the LES of each specimen from organ donors and from the EB, 5 cm above the transitional line (8,12). The weight of the strips was similar in the three regions studied: 1) clasp, 0.29 Ϯ 0.01 g (n ϭ 18); 2) sling, 0.31 Ϯ 0.02 g (n ϭ 13); and 3) EB, 0.31 Ϯ 0.02 g (n ϭ 28).…”

Section: Preparationsmentioning

confidence: 99%

“…The Krebs solution used in these experiments was the same as in our laboratory's previous studies (7,8,12). Sodium nitroprusside (SNP), nicotine, nifedipine, tetrodotoxin (TTX), the selective P2X subtype receptor agonist ␣,␤-methyleneadenosine 5=-triphosphate (␣,␤-meATP), the P2Y 1 receptor agonist adenosine-5=-[␤-thio] diphosphate trilithium salt (ADP␤S), N -nitro-L-arginine (L-NNA), ␣-chymotrypsin, and VIP were obtained from Sigma Chemical (St. Louis, MO).…”

Section: Solutions and Drugsmentioning

confidence: 99%

“…Changes in tension of the strips were measured using isometric force transducers (model 03 Force Transducer and model 7 Series Polygraph, respectively, Grass Instruments, Quincy, MA), computed using the data acquisition software Acqknowledge 3.7.2 (Biopac Systems). After an equilibration period of 60 min, strips were stretched up to 150% of their initial length and positioned between two parallel platinum wire electrodes 10 mm apart (7,8,12). Thereafter, strips taken from the LES progressively increased their tone during the following 1-2 h, and those from the EB did not.…”

Section: Techniquesmentioning

confidence: 99%

“…The macroscopic arrangement of LES inner muscle circular smooth fibers in humans and pigs is very similar, with semicircular transverse muscle clasps on the lesser curve side ("clasp fibers") and long oblique gastric "sling" fibers in the greater curvature on the left side of LES (17,36). Porcine LES shows a strong transversal functional asymmetry, as neural stimulation induces stronger nitrergic responses and weaker cholinergic responses in clasp fibers and, in contrast, weaker nitrergic responses and stronger cholinergic responses in the sling region (8). A very recent study on mice also found regional differences in the inhibitory junction potential (IJP) between clasp and sling LES sides (41).…”

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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: 92%

Section: Preparationsmentioning

confidence: 99%

Section: Solutions and Drugsmentioning

confidence: 99%

Section: Techniquesmentioning

confidence: 99%

mentioning

confidence: 99%

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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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Generation of Spontaneous Tone by Gastrointestinal Sphincters

Keef

Cobine

2019

Advances in Experimental Medicine and Biology

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A study on the congruence and proximity of the sling and clasp fibres at the cardio-esophageal junction of the stomach

Chandrupatla,

Susai

2023

Surg Radiol Anat

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Background and Aim: The cardio-esophageal sphincter that is located in close longitudinal proximity to the origin of the lesser curvature of the stomach has a unique pattern of external muscle bres whose inner oblique layer would normally form an elongated sling and the middle partially circular layer would form a projecting clasp into the already existing muscular sling of the former congruently, which would result in the formation of an anatomical sphincter in that area that would normally be devoid of the external longitudinal muscle layer coat. Certain authors have disagreed with the notion of this standard literature and have proposed that the clasp and sling bres need not necessarily be congruent and may even remain independent of each other with partial contributions from the longitudinal muscle layers as well that may arise tangentially in different populations, which may in turn contribute to re ux esophagitis in that population. Hence, the clasp and sling bre muscular patterns were observed in six formalin-embalmed cadavers at the department of anatomy in a tertiary care institute as part of routine dissections in series, and the ndings were then reported.Findings: At the junction of the lesser curvature of the stomach with the oesophagus, all 6 cadavers showed a longitudinal sling pattern as opposed to the conventional oblique sling. The circular muscle layer was found to be merged with the outer longitudinal muscle layer to form the sling that pulled away from the clasp, resulting in a loss of congruency for the same. The clasp bres, however, were found to be contributed by the inner oblique muscle layer. The conventional perpendicular or tangential merging of the clasp with the sling was not observed; instead, an obtuse, blunt angular merging of the clasp with the sling was observed.Discussion -The deviation of the sling from the clasp could indicate a lack of a proper t between them at the cardioesophageal sphincter. The lack of robustness in the attachment of the clasp to the sling may possibly contribute to the diminished taut pull of the clasp in this subset of the population. These would be signi cant determinants for a predisposition to re ux esophagitis and Barrett's oesophagus.

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Mechanisms controlling function in the clasp and sling regions of porcine lower oesophageal sphincter

Abstract: Clasp and sling fibres of the porcine LOS show marked intrinsic functional differences. This should be considered when developing more specific approaches to human LOS motility disorders.

Cited by 21 publications

References 33 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

Generation of Spontaneous Tone by Gastrointestinal Sphincters

A study on the congruence and proximity of the sling and clasp fibres at the cardio-esophageal junction of the stomach

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