Ava[l-Pro9,N-MeLeu10] Substance P(7-11) (GR 73632) and Sar9, Met(O2)11Increase Distention-Induced Peristalsis through Activation of Neurokinin-1 Receptors on Smooth Muscle and Interstitial Cells of Cajal

Nieuwmeyer, Florentine; Ye, Jing; Huizinga, Jan D.

doi:10.1124/jpet.105.094920

Cited by 16 publications

(9 citation statements)

References 41 publications

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“…However, it cannot be excluded that some of the SP-IR nerve endings abutting on ICC-DMP are sensory. This hypothesis is not in contrast with data recently obtained in a functional study which demonstrates that activation of NK1r on the ileal ICC results in an increase in slow wave frequency and distension-induced peristaltic activity [83]. In many cases, NK1 receptors may mediate action on ICC and no indirect innervation of smooth muscle cells.…”

Section: Icc and Sp-ir Nerve Fiberscontrasting

confidence: 71%

Relationships between neurokinin receptor‐expressing interstitial cells of Cajal and tachykininergic nerves in the gut

Faussone–Pellegrini

2006

J Cellular Molecular Medi

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The so-called interstitial cells of Cajal (ICC) are distributed throughout the muscle coat of the alimentary tract with characteristic intramural location and species-variations in structure and staining. Several ICC sub-types have been identified: ICC-DMP, ICC-MP, ICC-IM, ICC-SM. Gut motility is regulated by ICC and each sub-type is responsible for the electrical activities typical of each gut region and/or muscle layer. The interstitial position of the ICC between nerve endings and smooth muscle cells has been extensively considered. Some of these nerve endings contain tachykinins. Three distinct tachykinin receptors (NK1r, NK2r and NK3r) have been demonstrated by molecular biology. Each of them binds with different affinities to a series of tachykinins (SP, NKA and NKB). In the ileum, SP-immunoreactive (SP-IR) nerve fibers form a rich plexus at the deep muscular plexus (DMP), distributed around SP-negative cells, and ICC-DMP intensely express the SP-preferred receptor NK1r; conversely a faint NK1r-IR is detected on the ICC-MP and mainly after receptor internalization was induced by agonists. ICC-IM are never stained in laboratory mammals, while those of the human antrum are NK1r-IR. RT-PCR conducted on isolated ileal ICC-MP and gastric ICC-IM showed that these cells express NK1r and NK3r. Colonic ICC, except those in humans, do not express NK1r-IR, at least in resting conditions. Outside the gut, NK1r-IR cells were seen in the arterial wall and exocrine pancreas. In the mouse gut only, NK1r-IR is present in non-neuronal cells located within the intestinal villi, so-called myoid cells, which are c-kit-negative and α-smooth muscle actin-positive. Immunohistochemistry and functional studies confirmed that ICC receive input from SP-IR terminals, with differences between ICC sub-types. In the rat, very early after birth, NK1r is expressed by the ICC-DMP and SP by the related nerve varicosities. Studies on pathological conditions are few and those on mutant strains practically absent. It has only been reported that in the inflamed ileum of rats the NK1r-IR ICC-DMP disappear and that at the peak of inflammatory conditions ICC-MP are NK1r-IR. In the ileum of mice with a mutation in the W locus, ICC-DMP were seen to express c-kit-IR but not NK1-IR, and SP-IR innervation seems unchanged. In summary, there are distinct ICC populations, each of them under a different tachykininergic control and, likely, having different functions. Further studies are recommended at the aim of understanding ICC involvement in modulating/transmitting tachykininergic inputs.

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Section: Icc and Sp-ir Nerve Fiberscontrasting

confidence: 71%

Relationships between neurokinin receptor‐expressing interstitial cells of Cajal and tachykininergic nerves in the gut

Faussone–Pellegrini

2006

J Cellular Molecular Medi

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“…In the cat intestine, acetylcholine-induced slow waves have been reported to occur in early studies (Dahms et al, 1987) and Bolton has extensively studied acetylcholine-induced slow waves in the guinea pig ileum (Bolton, 1971). Interestingly rhythmic low and high frequency propagating motor activity is very often encountered (Ehrlein et al, 1987; Nieuwmeyer et al, 2006) and we have preliminary data that suggests that the proposed theory of independent but cooperating ICC pacemaker systems may also apply to the small intestine (Huizinga and Kunze, unpublished).…”

Section: Discussionmentioning

confidence: 50%

Two Independent Networks of Interstitial Cells of Cajal Work Cooperatively with the Enteric Nervous System to Create Colonic Motor Patterns

Huizinga¹,

Martz²,

Gil³

et al. 2011

Front. Neurosci.

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129

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Normal motility of the colon is critical for quality of life and efforts to normalize abnormal colon function have had limited success. A better understanding of control systems of colonic motility is therefore essential. We report here a hypothesis with supporting experimental data to explain the origin of rhythmic propulsive colonic motor activity induced by general distention. The theory holds that both networks of interstitial cells of Cajal (ICC), those associated with the submuscular plexus (ICC–SMP) and those associated with the myenteric plexus (ICC–MP), orchestrate propagating contractions as pacemaker cells in concert with the enteric nervous system (ENS). ICC–SMP generate an omnipresent slow wave activity that causes propagating but non-propulsive contractions (“rhythmic propagating ripples”) enhancing absorption. The ICC–MP generate stimulus-dependent cyclic depolarizations propagating anally and directing propulsive activity (“rhythmic propulsive motor complexes”). The ENS is not essential for both rhythmic motor patterns since distention and pharmacological means can produce the motor patterns after blocking neural activity, but it supplies the primary stimulus in vivo. Supporting data come from studies on segments of the rat colon, simultaneously measuring motility through spatiotemporal mapping of video recordings, intraluminal pressure, and outflow measurements.

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“…Their cyclical pattern suggests that enteric circuits are able to generate bouts of activity at ϳ1-min intervals. Motor patterns with cycle periods in this range have been described in the small intestine of several animal species, with several terminologies such as minute rhythm, intermittent, fatigued, repetitive, or rhythmic activity both in vivo (20,25,43) and ex vivo (26,38,51). Whether such cyclic events may also have some myogenic component in humans remains to be established (28).…”

Section: Neural Circuits Underlying the Propagating Discrete Clusterementioning

confidence: 99%

Neurally mediated propagating discrete clustered contractions superimposed on myogenic ripples in ex vivo segments of human ileum

Kuizenga

Sia

Dodds

et al. 2015

American Journal of Physiology-Gastrointestinal and Liver Physi

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Kuizenga MH, Sia TC, Dodds KN, Wiklendt L, Arkwright JW, Thomas A, Brookes SJ, Spencer NJ, Wattchow DA, Dinning PG, Costa M. Neurally mediated propagating discrete clustered contractions superimposed on myogenic ripples in ex vivo segments of human ileum. Am J Physiol Gastrointest Liver Physiol 308: G1-G11, 2015. First published November 13, 2014; doi:10.1152/ajpgi.00230.2014.-Narrow muscle strips have been extensively used to study intestinal contractility. Larger specimens from laboratory animals have provided detailed understanding of mechanisms that underlie patterned intestinal motility. Despite progress in animal tissue, investigations of motor patterns in large, intact specimens of human gut ex vivo have been sparse. In this study, we tested whether neurally dependent motor patterns could be detected in isolated specimens of intact human ileum. Specimens (n ϭ 14; 7-30 cm long) of terminal ileum were obtained with prior informed consent from patients undergoing colonic surgery for removal of carcinomas. Preparations were set up in an organ bath with an array of force transducers, a fiberoptic manometry catheter, and a video camera. Spontaneous and distension-evoked motor activity was recorded, and the effects of lidocaine, which inhibits neural activity, were studied. Myogenic contractions (ripples) occurred in all preparations (6.17 Ϯ 0.36/min). They were of low amplitude and formed complex patterns by colliding and propagating in both directions along the specimen at anterograde velocities of 4.1 Ϯ 0.3 mm/s and retrogradely at 4.9 Ϯ 0.6 mm/s. In five specimens, larger amplitude clusters of contractions were seen (discrete clustered contractions), which propagated aborally at 1.05 Ϯ 0.13 mm/s and orally at 1.07 Ϯ 0.09 mm/s. These consisted of two to eight phasic contractions that aligned with ripples. These motor patterns were abolished by addition of lidocaine (0.3 mM). The ripples continued unchanged in the presence of this neural blocking agent. These results demonstrate that both myogenic and neurogenic motor patterns can be studied in isolated specimens of human small intestine. small intestine; motor patterns; enteric nervous system; myogenic; neurogenic PROPULSION AND MIXING OF INTESTINAL CONTENTS along the digestive tract are essential for normal digestion. The motor patterns underlying these functions are due to the coordinated contractions and relaxations of the smooth muscle layers of the intestine. The internal circular smooth muscle layer and the external longitudinal smooth muscle layer are controlled by two main mechanisms. Myogenic activity is driven by the nonneural pacemaker cells, the interstitial cells of Cajal. Neurogenic control is mediated by circuits in the enteric nervous system. These two types of activity combine to generate the motor patterns that mix and propel luminal content (14,29). Most of our understanding of these mechanisms has been derived from animal studies. Although the basic functions of the gastrointestinal tract are similar between human and animals, there are si...

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Ava[l-Pro⁹,N-MeLeu10] Substance P(7-11) (GR 73632) and Sar⁹, Met(O₂)¹¹Increase Distention-Induced Peristalsis through Activation of Neurokinin-1 Receptors on Smooth Muscle and Interstitial Cells of Cajal

Cited by 16 publications

References 41 publications

Relationships between neurokinin receptor‐expressing interstitial cells of Cajal and tachykininergic nerves in the gut

Relationships between neurokinin receptor‐expressing interstitial cells of Cajal and tachykininergic nerves in the gut

Two Independent Networks of Interstitial Cells of Cajal Work Cooperatively with the Enteric Nervous System to Create Colonic Motor Patterns

Neurally mediated propagating discrete clustered contractions superimposed on myogenic ripples in ex vivo segments of human ileum

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