Colonic migrating motor complexes (CMMCs) in the isolated mouse colon

Fida, Rosa; Lyster, D. J. K.; Bywater, Robert A.R.; Taylor, Grahame S.

doi:10.1046/j.1365-2982.1997.d01-25.x

Cited by 107 publications

(186 citation statements)

References 15 publications

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“…12 The present study deals with propulsive motor patterns in the rat colon. Colonic propulsive contractions are often referred to as "colonic migrating motor complexes (CMMCs)" described as such in the rat 13,14 and mouse [15][16][17] colon. We and others recently reported that the CMMC contains 2 distinct propulsive motor patterns, a pancolonic long distance contraction (LDC) and a rhythmic propagating motor complex (RPMC) that is primarily observed in the mid and distal colon.…”

Section: Introductionmentioning

confidence: 99%

Neurotensin Changes Propulsive Activity into a Segmental Motor Pattern in the Rat Colon

Chen

Yang

et al. 2016

J Neurogastroenterol Motil

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Background/AimsNeurotensin is a gut-brain peptide with both inhibitory and excitatory actions on the colonic musculature; our objective was to understand the implications of this for motor patterns occurring in the intact colon of the rat. MethodsThe effects of neurotensin with concentrations ranging from 0.1-100 nM were studied in the intact rat colon in vitro, by investigating spatio-temporal maps created from video recordings of colonic motility before and after neurotensin. ResultsLow concentration of neurotensin (0.1-1 nM) inhibited propagating long distance contractions and rhythmic propagating motor complexes; in its place a slow propagating rhythmic segmental motor pattern developed. The neurotensin receptor 1 antagonist SR-48692 prevented the development of the segmental motor pattern. Higher concentrations of neurotensin (10 nM and 100 nM) were capable of restoring long distance contraction activity and inhibiting the segmental activity. The slow propagating segmental contraction showed a rhythmic contraction --relaxation cycle at the slow wave frequency originating from the interstitial cells of Cajal associated with the myenteric plexus pacemaker. High concentrations given without prior additions of low concentrations did not evoke the segmental motor pattern. These actions occurred when neurotensin was given in the bath solution or intraluminally. The segmental motor pattern evoked by neurotensin was inhibited by the neural conduction blocker lidocaine. ConclusionsNeurotensin (0.1-1 nM) inhibits the dominant propulsive motor patterns of the colon and a distinct motor pattern of rhythmic slow propagating segmental contractions develops. This motor pattern has the hallmarks of haustral boundary contractions. (J Neurogastroenterol Motil 2016;22:517-528)

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Section: Introductionmentioning

confidence: 99%

Neurotensin Changes Propulsive Activity into a Segmental Motor Pattern in the Rat Colon

Chen

Yang

et al. 2016

J Neurogastroenterol Motil

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“…However, recent developments allow some conclusions to be drawn. Isolated mouse intestine and colon exhibit periodic strong contraction complexes that propagate along the segment in a manner analogous to phase III contractions of interdigestive MMCs [132][133][134][135]. This similarity is so strong that the colonic propagating contraction complexes are usually termed colonic MMCs, although they may actually be analogues of mass-movement contractions involved in defecation.…”

Section: Functional Roles Of Purinergic Ijpsmentioning

confidence: 99%

Purinergic mechanisms in the control of gastrointestinal motility

Bornstein

2007

Purinergic Signalling

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For many years, ATP and adenosine have been implicated in movement regulation of the gastrointestinal tract. They act through three major receptor subtypes: adenosine or P1 receptors, P2X receptors and P2Y receptors. Each of these major receptor types can be subdivided into several different classes and is widely distributed amongst various neurons, muscle types, glia and interstitial cells that regulate intestinal functions. Several key roles for the different receptors and their endogenous ligands have been identified in physiological and pharmacological studies. For example, adenosine acting at A 1 receptors appears to inhibit intestinal motility in various pathological conditions. Similarly, ATP acting at P2Y receptors is an important component of inhibitory neuromuscular transmission, acting as a cotransmitter with nitric oxide. ATP acting at P2X and P2Y 1 receptors is important for synaptic transmission in simple descending excitatory and inhibitory reflex pathways. Some P2Y receptor subtypes prefer uridine nucleotides over purine nucleotides. Thus, roles for UTP and UDP as enteric transmitters in place of ATP cannot be excluded. ATP also appears to be important for sensory transduction, especially in chemosensitive pathways that initiate local inhibitory reflexes. Despite this evidence, data are lacking about the roles of either adenosine or ATP in more complex motility patterns such as segmentation or the interdigestive migrating motor complex. Clarification of roles for purinergic transmission in these common, but understudied, motility patterns will depend on the use of subtype-specific antagonists that in some cases have not yet been developed.

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“…22 This toxin abolishes CMMCs generated by enteric motor nerve activity. 23 We found that TTX mimicked the functional effects of narcoleptic IgG in this isolated organ preparation. Our results are consistent with a model in which an Ab in patients with narcolepsy blocks neurotransmission of both excitatory and inhibitory enteric motor nerves.…”

mentioning

confidence: 91%

“…23 Therefore, we investigated whether TTX could mimic the actions of the narcoleptic IgG. In colonic preparations undergoing CMMC activity, addition of 0.6 mmol/l TTX abolished CMMCs and increased smooth muscle resting tension (Figure 4a).…”

Section: Ttx Mimics the Effect Of Narcoleptic Iggmentioning

confidence: 99%

“…As observed in the parallel experiments with narcoleptic IgG (Figure 3), atropine (1 mmol/l) reversed the neostigmine-mediated increase in smooth muscle tension (Figure 4a and b). Thus, TTX, an ion channel blocker that binds both excitatory and inhibitory motor neurons in CMMCs, 23 mimics the physiological effects of the narcoleptic IgG on the CMMC bioassay. …”

Section: Ttx Mimics the Effect Of Narcoleptic Iggmentioning

confidence: 99%

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Potentiation of a functional autoantibody in narcolepsy by a cholinesterase inhibitor

Jackson

Spencer

Reed

et al. 2009

Laboratory Investigation

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We have recently reported the presence of an immunoglobulin G (IgG) autoantibody (Ab) in patients with narcolepsy with cataplexy that abolishes spontaneous colonic migrating motor complexes (CMMCs) and increases smooth muscle tension and atropine-sensitive phasic contractions in a physiological assay of an isolated colon. In this study, we used the cholinesterase inhibitor, neostigmine, to explore the mechanism of the narcoleptic IgG-mediated disruption of enteric motor function in four patients with narcolepsy with cataplexy and to identify a pharmacological mimic of the Ab. Neostigmine potentiated the narcoleptic IgG-mediated increase in smooth muscle resting tension and phasic smooth muscle contractions by an atropine-sensitive mechanism but exerted no effect on resting tension in the presence of control IgG. Decreased frequency of CMMCs mediated by IgG with anti-M3R activity was reversed by neostigmine. Therefore, a challenge with a cholinesterase inhibitor improves the specificity of the CMMC assay for narcoleptic IgG. Tetrodotoxin (TTX), a neuronal sodium channel blocker, also abolished CMMCs and increased resting tone, and a similar potentiation was observed with neostigmine; thus, TTX is a mimic of the functional effects of the narcoleptic IgG in this bioassay. These findings provide a link to pharmacological studies of canine narcolepsy and are consistent with a functional blockade of both excitatory and inhibitory motor neurons by the narcoleptic Ab, similar to the TTX mimic, presumably by binding to an autoantigenic target expressed in both populations of neurons.

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Colonic migrating motor complexes (CMMCs) in the isolated mouse colon

Cited by 107 publications

References 15 publications

Neurotensin Changes Propulsive Activity into a Segmental Motor Pattern in the Rat Colon

Neurotensin Changes Propulsive Activity into a Segmental Motor Pattern in the Rat Colon

Purinergic mechanisms in the control of gastrointestinal motility

Potentiation of a functional autoantibody in narcolepsy by a cholinesterase inhibitor

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