Neuroeffector apparatus in gastrointestinal smooth muscle organs

Sanders, Kenton M.; Hwang, Sung Jin; Ward, Sean M.

doi:10.1113/jphysiol.2010.196030

Cited by 135 publications

(136 citation statements)

References 82 publications

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“…Recently, the ICC, which is known to regulate spontaneous contraction by generating slow waves in the smooth muscle of the gastrointestinal tract, has been increasingly studied. 17,[26][27][28][29][30][31][32][33][34][35][36] Many studies have reported that ICC injury plays an important role in various chronic diseases that cause abnormal gastrointestinal contractions. 27,[29][30][31][32][33]35 In addition, it has been reported that spontaneous contraction signals are transmitted by ICC networks and that the loss of small intestinal motility in humans was caused by reduction in the ICC networks.…”

Section: Discussionmentioning

confidence: 99%

Alterations of Colonic Contractility in an Interleukin-10 Knockout Mouse Model of Inflammatory Bowel Disease

Park

Kwon

Kim

et al. 2015

J Neurogastroenterol Motil

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Background/Aims Inflammatory bowel disease is commonly accompanied by colonic dysmotility and causes changes in intestinal smooth muscle contractility. In this study, colonic smooth muscle contractility in a chronic inflammatory condition was investigated using smooth muscle tissues prepared from interleukin-10 knockout (IL-10 −/− ) mice. Methods Prepared smooth muscle sections were placed in an organ bath system. Cholinergic and nitrergic neuronal responses were observed using carbachol and electrical field stimulation with L-NG-nitroarginine methyl ester (L-NAME). The expression of interstitial cells of Cajal (ICC) networks, muscarinic receptors, neuronal nitric oxide synthase (nNOS) and inducible nitric oxide synthase (iNOS) was observed via immunofluorescent staining. Results The spontaneous contractility and expression of ICC networks in the proximal and distal colon was significantly decreased in IL-10 −/− mice compared to IL-10 +/+ mice. The contractility in response to carbachol was significantly decreased in the proximal colon of IL-10 −/− mice compared to IL-10 +/+ mice, but no significant difference was found in the distal colon. In addition, the expression of muscarinic receptor type 2 was reduced in the proximal colon of IL-10 −/− mice. The nictric oxide-mediated relaxation after electrical field stimulation was significantly decreased in the proximal and distal colon of IL-10 −/− mice. In inflamed colon, the expression of nNOS decreased, whereas the expression of iNOS increased. Conclusions These results suggest that damage to the ICC network and NOS system in the proximal and distal colon, as well as damage to the smooth muscle cholinergic receptor in the proximal colon may play an important role in the dysmotility of the inflamed colon.

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Section: Discussionmentioning

confidence: 99%

Alterations of Colonic Contractility in an Interleukin-10 Knockout Mouse Model of Inflammatory Bowel Disease

Park

Kwon

Kim

et al. 2015

J Neurogastroenterol Motil

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“…It should be emphasized, however, that these are largely integrated responses to released neurotransmitter(s) and/or their bioactive metabolites, that could be significantly affected by the desensitization of postjunctional receptors, modification of the driving forces for membrane currents, or rapid degradation of released purines (47). Such effects likely represent integrated responses of an effector syncytium that is composed of postjunctional cell targets electrically coupled with neighboring cells of the same or distinct cell types (18,46,49). Furthermore, commonly used pharmacological tools (i.e., synthetic receptor agonists and antagonists, enzyme inhibitors or stable ATP analogues) may not have sufficient selectivity or may not demonstrate the same receptor specificity as the endogenous neurotransmitter.…”

Section: Caveats Of Using Postjunctional Responses To Nerve Stimulatimentioning

confidence: 99%

“…Multiple purines are present in the cytosol and subcellular organelles and could potentially be released upon depolarizing or other stimuli. Finally, released transmitters can affect various cell targets (18) leading to complex tissue responses. All these factors contribute to the considerable complexity of purine regulation of smooth muscle.…”

Section: Functional Complexity Of Smooth Musclementioning

confidence: 99%

Neuronal and extraneuronal release of ATP and NAD⁺ in smooth muscle

Mutafova‐Yambolieva¹

2012

IUBMB Life

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SUMMARYAdenosine 5′-triphosphate (ATP) and nicotinamide adenine dinucleotide (NAD + ) are key intracellular constituents involved in energy transfer and redox homeostasis in the cell. ATP is also released in the extracellular space and in the past half century it has been assumed to be the purinergic neurotransmitter in many systems including smooth muscle. In some smooth muscles (i.e., the human urinary bladder detrusor muscle) ATP does appear to be primarily released from nerves upon action potential firings, but in other smooth muscles (i.e., the human large intestine) ATP does not mimic the endogenous purine neurotransmitter. It was recently found that NAD + , another ubiquitous intracellular adenine nucleotide, also follows a regulated release in neurosecretory cells, vascular and visceral smooth muscles, and the brain. In some cases NAD + fulfills pre-and postsynaptic criteria for a neurotransmitter better than ATP. Therefore, the purine hypothesis of neural regulation in smooth muscle is in need of reevaluation. This article will briefly review the current understanding of neuronal and extraneuronal release of purines in smooth muscle with emphasis on the roles of extracellular ATP and NAD + , and, further, will discuss more recent information about the likely involvement of multiple purines in smooth muscle neurotransmission.

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“…Whether neuronal input to ICC is significant is a matter of debate, [1][2][3][4][5][6][7]17,26 however growing evidence suggests that ICC play a role in enteric neurotransmission. It has been shown that intramuscular ICC is closely associated with myenteric motor neurons, forming synapse-like junctions with nerve varicosities.…”

Section: Gastrointestinal Motilitymentioning

confidence: 99%

“…1 Currently under debate is the exact role and significance of ICC in enteric neurotransmission. [1][2][3][4][5][6][7] Enteric neurons utilize acetylcholine as their primary neurotransmitter, 8 and anticholinergic drugs are well known to block enteric neurotransmission and result in GI adverse effects, including constipation. 9,10 What is as yet unknown is the effect of anticholinergic drugs on the background rhythmic contractions driven by slow waves.…”

Section: Introductionmentioning

confidence: 99%

Analysis of spatiotemporal pattern and quantification of gastrointestinal slow waves caused by anticholinergic drugs

et al. 2017

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ABSTRACT. Anticholinergic drugs are well-known to cause adverse effects, such as constipation, but their effects on baseline contractile activity in the gut driven by slow waves is not well established. In a video-based gastrointestinal motility monitoring (GIMM) system, a mouse's small intestine was placed in Krebs solution and recorded using a high definition camera. Untreated controls were recorded for each specimen, then treated with a therapeutic concentration of the drug, and finally, treated with a supratherapeutic dose of the drug. Next, the video clips showing gastrointestinal motility were processed, giving us the segmentation motions of the intestine, which were then converted via Fast Fourier Transform (FFT) into their respective frequency spectrums. These contraction quantifications were analyzed from the video recordings under standardised conditions to evaluate the effect of drugs. Six experimental trials were included with benztropine and promethazine treatments. Only the supratherapeutic dose of benztropine was shown to significantly decrease the amplitude of contractions; at therapeutic doses of both drugs, neither frequency nor amplitude was significantly affected. We have demonstrated that intestinal slow waves can be analyzed based on the colonic frequency or amplitude at a supratherapeutic dose of the anticholinergic medications. More research is required on the effects of anticholinergic drugs on these slow waves to ascertain the true role of ICC in neurologic control of gastrointestinal motility.

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Neuroeffector apparatus in gastrointestinal smooth muscle organs

Abstract: Control of gastrointestinal (GI) movements by enteric motoneurons is

Cited by 135 publications

References 82 publications

Alterations of Colonic Contractility in an Interleukin-10 Knockout Mouse Model of Inflammatory Bowel Disease

Alterations of Colonic Contractility in an Interleukin-10 Knockout Mouse Model of Inflammatory Bowel Disease

Neuronal and extraneuronal release of ATP and NAD⁺ in smooth muscle

Analysis of spatiotemporal pattern and quantification of gastrointestinal slow waves caused by anticholinergic drugs

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Neuroeffector apparatus in gastrointestinal smooth muscle organs

Abstract: Control of gastrointestinal (GI) movements by enteric motoneurons is

Cited by 135 publications

References 82 publications

Alterations of Colonic Contractility in an Interleukin-10 Knockout Mouse Model of Inflammatory Bowel Disease

Alterations of Colonic Contractility in an Interleukin-10 Knockout Mouse Model of Inflammatory Bowel Disease

Neuronal and extraneuronal release of ATP and NAD+ in smooth muscle

Analysis of spatiotemporal pattern and quantification of gastrointestinal slow waves caused by anticholinergic drugs

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Product

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Neuronal and extraneuronal release of ATP and NAD⁺ in smooth muscle