Different responsiveness of excitatory and inhibitory enteric motor neurons in the human esophagus to electrical field stimulation and to nicotine

2004 ◽  
Vol 287 (1) ◽  
pp. G299-G306 ◽  
Author(s):  
Asensio A. González ◽  
Ricard Farré ◽  
Pere Clavé

To compare electrical field stimulation (EFS) with nicotine in the stimulation of excitatory and inhibitory enteric motoneurons (EMN) in the human esophagus, circular lower esophageal sphincter (LES), and circular and longitudinal esophageal body (EB) strips from 20 humans were studied in organ baths. Responses to EFS or nicotine (100 μM) were compared in basal conditions, after NG-nitro-l-arginine (l-NNA; 100 μM), and after l-NNA and apamin (1 μM). LES strips developed myogenic tone enhanced by TTX (5 μM) or l-NNA. EFS-LES relaxation was abolished by TTX, unaffected by hexamethonium (100 μM), and enhanced by atropine (3 μM). Nicotine-LES relaxation was higher than EFS relaxation, reduced by TTX or atropine, and blocked by hexamethonium. After l-NNA, EFS elicited a strong cholinergic contraction in circular LES and EB, and nicotine elicited a small relaxation in LES and no contractile effect in EB. After l-NNA and apamin, EFS elicited a strong cholinergic contraction in LES and EB, and nicotine elicited a weak contraction amounting to 6.64 ± 3.19 and 9.20 ± 5.51% of that induced by EFS. EFS elicited a contraction in longitudinal strips; after l-NNA and apamin, nicotine did not induce any response. Inhibitory EMN tonically inhibit myogenic LES tone and are efficiently stimulated both by EFS and nicotinic acetylcholine receptors (nAChRs) located in somatodendritic regions and nerve terminals, releasing nitric oxide and an apamin-sensitive neurotransmitter. In contrast, although esophageal excitatory EMN are efficiently stimulated by EFS, their stimulation through nAChRs is difficult and causes weak responses, suggesting the participation of nonnicotinic mechanisms in neurotransmission to excitatory EMN in human esophagus.

1999 ◽  
Vol 277 (3) ◽  
pp. G548-G554 ◽  
Author(s):  
Aliye Uc ◽  
S. T. Oh ◽  
Joseph A. Murray ◽  
Eugene Clark ◽  
Jeffrey L. Conklin

Vasoactive intestinal polypeptide (VIP) and nitric oxide (NO ⋅) are thought to mediate lower esophageal sphincter (LES) relaxation. Transverse muscle strips from the opossum LES were used to test this hypothesis. Electrical field stimulation (EFS) produced a biphasic LES relaxation: a rapid component during the stimulus was more prominent at lower stimulus frequencies, and a sustained component was more prominent at higher frequencies. N ω-nitro-l-arginine and hemoglobin inhibited the rapid component but affected the sustained component less. Exogenous VIP decreased LES tone. A number of purported VIP antagonists blocked neither VIP-induced nor EFS-induced relaxation of the LES. The calcitonin gene-related peptide (CGRP) antagonist CGRP-(8—37) did not alter EFS-induced LES relaxation. EFS-induced relaxation of opossum LES muscle is biphasic, and the initial, rapid component of the relaxation is mediated primarily by NO ⋅. The mediator of the sustained component was not identified.


2011 ◽  
Vol 300 (5) ◽  
pp. G782-G794 ◽  
Author(s):  
B. Lecea ◽  
D. Gallego ◽  
R. Farré ◽  
A. Opazo ◽  
M. Aulí ◽  
...  

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 Nω-nitro-l-arginine (l-NNA) shifted the EFS “on”-relaxation to an “off”-relaxation, partly antagonized by 10 μM 2′-deoxy- N6-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 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 P2Y1receptors) and vasoactive intestinal peptide-mediating part of nonnitrergic clasp LES relaxation.


2006 ◽  
Vol 290 (3) ◽  
pp. G486-G495 ◽  
Author(s):  
Abigail S. Forrest ◽  
Tamás Ördög ◽  
Kenton M. Sanders

Gastric peristaltic contractions are driven by electrical slow waves modulated by neural and humoral inputs. Excitatory neural input comes primarily from cholinergic motor neurons, but ACh causes depolarization and chronotropic effects that might disrupt the normal proximal-to-distal spread of gastric slow waves. We used intracellular electrical recording techniques to study cholinergic responses in stomach tissues from wild-type and W/W V mice. Electrical field stimulation (5 Hz) enhanced slow-wave frequency. These effects were abolished by atropine and the muscarinic M3-receptor antagonist 4-diphenylacetoxy- N-methylpiperidine methiodide. ACh released from nerves did not depolarize antral muscles. At higher rates of stimulation (10 Hz), chronotropic effects were mediated by ACh and a noncholinergic transmitter and blocked by muscarinic antagonists and neurokinin (NK1 and NK2)-receptor antagonists. Neostigmine enhanced slow-wave frequency, suggesting that the frequency of antral pacemakers is kept low by efficient metabolism of ACh. Neostigmine had no effect on slow-wave frequency in muscles of W/W v mice, which lack intramuscular interstitial cells of Cajal (ICC-IM). These muscles also showed no significant chronotropic response to 5-Hz electrical field stimulation or the cholinergic agonist carbachol. The data suggest that the chronotropic effects of cholinergic nerve stimulation occur via ICC-IM in the murine stomach. The capacity of gastric muscles to metabolize ACh released from enteric motor neurons contributes to the maintenance of the proximal-to-distal slow-wave frequency gradient in the murine stomach. ICC-IM play a critical role in neural regulation of gastric motility, and ICC-IM become the dominant pacemaker cells during sustained cholinergic drive.


2020 ◽  
Vol 4 (2) ◽  
Author(s):  
Wei Li ◽  
Hefei Li ◽  
Zhenqing Sun ◽  
Ben Li ◽  
Qiang Guo ◽  
...  

In the first and second parts of this study, 5-hydroxytryptamine (5HT) receptors, including 5-HT3 and 5-HT4 with the highest expression level, were found in clasp and sling fibres of the lower esophageal sphincter (LES). Specific 5-HT3 and 5-HT4 receptor agonists can induce the contraction effect of clasp and sling fibres of the LES while specific 5-HT7 receptor agonists showed no effects. In the study of this part, the in-vitro muscle tension measurement technology and EFS methods were used to detect the effect of the selective 5-HT receptor antagonist on the clasp and sling fibres of the in-vitro LES under the electrical field stimulation (EFS), and further to ensure the effect of 5-HT receptor in the LES neuroregulatory pathway, and deeply explore the effect of 5-HT receptor in the systolic and diastolic function regulation of the LES.


1989 ◽  
Vol 20 (5) ◽  
pp. 663-669 ◽  
Author(s):  
Carlo Alberto Maggi ◽  
Riccardo Patacchini ◽  
Paolo Santicioli ◽  
Damiano Turini ◽  
Gabriele Barbanti ◽  
...  

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