Experimental inflammation of the rat distal colon inhibits ion secretion in the proximal colon by affecting the enteric nervous system

AbstractHow the Enteric Nervous System (ENS) coordinates propulsion of content along the gastrointestinal (GI)-tract has been a major unresolved issue. We reveal a mechanism that explains how ENS activity underlies propulsion of content along the colon. We used a recently developed high-resolution video imaging approach with concurrent electrophysiological recordings from smooth muscle, during fluid propulsion. Recordings showed pulsatile firing of excitatory and inhibitory neuromuscular inputs not only in proximal colon, but also distal colon, long before the propagating contraction invades the distal region. During propulsion, wavelet analysis revealed increased coherence at ~2 Hz over large distances between the proximal and distal regions. Therefore, during propulsion, synchronous firing of descending inhibitory nerve pathways over long ranges aborally acts to suppress smooth muscle from contracting, counteracting the excitatory nerve pathways over this same region of colon. This delays muscle contraction downstream, ahead of the advancing contraction. The mechanism identified is more complex than expected and vastly different from fluid propulsion along other hollow smooth muscle organs; like lymphatic vessels, portal vein, or ureters, that evolved without intrinsic neurons.

Download Full-text

Optogenetic activation of the distal colon epithelium engages enteric nervous system circuits to initiate motility patterns

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.00026.2021 ◽

2021 ◽

Author(s):

Sarah A Najjar ◽

Brian Edwards ◽

Kathryn M. Albers ◽

Brian M Davis ◽

Kristen M Smith-Edwards

Keyword(s):

Nervous System ◽

Epithelial Cells ◽

Enteric Nervous System ◽

Large Scale ◽

Ex Vivo ◽

Distal Colon ◽

Proximal Colon ◽

Nerve Fibers ◽

Colon Motility ◽

Neural Communication

Background & Aims: Digestive functions of the colon depend on sensory-motor reflexes in the enteric nervous system (ENS), initiated by intrinsic primary afferent neurons (IPANs). IPAN terminals project to the mucosal layer of the colon, allowing communication with epithelial cells comprising the colon lining. The chemical nature and functional significance of this epithelial-neural communication in regards to secretion and colon motility are of high interest. Colon epithelial cells can produce and release neuroactive substances such as ATP and 5-HT, which can activate receptors on adjacent nerve fibers, including IPAN subtypes. In this study we examined if stimulation of epithelial cells alone is sufficient to activate neural circuits that control colon motility. Methods: Optogenetics and calcium imaging were used in ex vivo preparations of the mouse colon to selectively stimulate the colon epithelium, measure changes in motility and record activity of neurons within the myenteric plexus. Results: Light-mediated activation of epithelial cells lining the distal, but not proximal, colon caused local contractions and increased the rate of colonic migrating motor complexes. Epithelial-evoked local contractions in the distal colon were reduced by both ATP and 5-HT receptor antagonists. Conclusions: Our findings indicate that colon epithelial cells likely utilize purinergic and serotonergic signaling to initiate activity in myenteric neurons, produce local contractions and facilitate large-scale coordination of ENS activity responsible for whole-colon motility patterns.

Download Full-text

Distribution and function of monoacylglycerol lipase in the gastrointestinal tract

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.90500.2008 ◽

2008 ◽

Vol 295 (6) ◽

pp. G1255-G1265 ◽

Cited By ~ 40

Author(s):

Marnie Duncan ◽

Adam D. Thomas ◽

Nina L. Cluny ◽

Annie Patel ◽

Kamala D. Patel ◽

...

Keyword(s):

Nervous System ◽

Enteric Nervous System ◽

Distal Colon ◽

Proximal Colon ◽

Nerve Fibers ◽

Activity Levels ◽

Monoacylglycerol Lipase ◽

And Function ◽

Endogenous Cannabinoid ◽

Oxide Synthase

The endogenous cannabinoid system plays an important role in the regulation of gastrointestinal function in health and disease. Endocannabinoid levels are regulated by catabolic enzymes. Here, we describe the presence and localization of monoacylglycerol lipase (MGL), the major enzyme responsible for the degradation of 2-arachidonoylglycerol. We used molecular, biochemical, immunohistochemical, and functional assays to characterize the distribution and activity of MGL. MGL mRNA was present in rat ileum throughout the wall of the gut. MGL protein was distributed in the muscle and mucosal layers of the ileum and in the duodenum, proximal colon, and distal colon. We observed MGL expression in nerve cell bodies and nerve fibers of the enteric nervous system. There was extensive colocalization of MGL with PGP 9.5 and calretinin-immunoreactive neurons, but not with nitric oxide synthase. MGL was also present in the epithelium and was highly expressed in the small intestine. Enzyme activity levels were highest in the duodenum and decreased along the gut with lowest levels in the distal colon. We observed both soluble and membrane-associated enzyme activities. The MGL inhibitor URB602 significantly inhibited whole gut transit in mice, an action that was abolished in cannabinoid 1 receptor-deficient mice. In conclusion, MGL is localized in the enteric nervous system where endocannabinoids regulate intestinal motility. MGL is highly expressed in the epithelium, where this enzyme may have digestive or other functions yet to be determined.

Download Full-text

Melatonin inhibits prostaglandin E2- and sodium nitroprusside-induced ion secretion in rat distal colon

European Journal of Pharmacology ◽

10.1016/j.ejphar.2007.11.031 ◽

2008 ◽

Vol 581 (1-2) ◽

pp. 164-170 ◽

Cited By ~ 14

Author(s):

Libor Mrnka ◽

Miroslav Hock ◽

Markéta Rybová ◽

Jiří Pácha

Keyword(s):

Prostaglandin E2 ◽

Sodium Nitroprusside ◽

Distal Colon ◽

Ion Secretion ◽

Rat Distal Colon

Download Full-text

Differential actions of urocortins on neurons of the myenteric division of the enteric nervous system in guinea pig distal colon

British Journal of Pharmacology ◽

10.1111/j.1476-5381.2009.00516.x ◽

2009 ◽

Vol 159 (1) ◽

pp. 222-236 ◽

Cited By ~ 23

Author(s):

S Liu ◽

W Ren ◽

M-H Qu ◽

GA Bishop ◽

G-D Wang ◽

...

Keyword(s):

Nervous System ◽

Guinea Pig ◽

Enteric Nervous System ◽

Distal Colon

Download Full-text

Diversity of neurogenic smooth muscle electrical rhythmicity in mouse proximal colon

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.00317.2019 ◽

2020 ◽

Vol 318 (2) ◽

pp. G244-G253 ◽

Cited By ~ 4

Author(s):

Nick J. Spencer ◽

Lee Travis ◽

Lukasz Wiklendt ◽

Timothy J. Hibberd ◽

Marcello Costa ◽

...

Keyword(s):

Nervous System ◽

Smooth Muscle ◽

Enteric Nervous System ◽

Extracellular Recording ◽

Proximal Colon ◽

Proximal Region ◽

Muscle Membrane ◽

Mouse Colon ◽

Cross Correlation Analysis

The mechanisms underlying electrical rhythmicity in smooth muscle of the proximal colon are incompletely understood. Our aim was to identify patterns of electrical rhythmicity in smooth muscle of the proximal region of isolated whole mouse colon and characterize their mechanisms of origin. Two independent extracellular recording electrodes were used to record the patterns of electrical activity in smooth muscle of the proximal region of whole isolated mouse colon. Cross-correlation analysis was used to quantify spatial coordination of these electrical activities over increasing electrode separation distances. Four distinct neurogenic patterns of electrical rhythmicity were identified in smooth muscle of the proximal colon, three of which have not been identified and consisted of bursts of rhythmic action potentials at 1–2 Hz that were abolished by hexamethonium. These neurogenic patterns of electrical rhythmicity in smooth muscle were spatially and temporally synchronized over large separation distances (≥2 mm rosto-caudal axis). Myogenic slow waves could be recorded from the same preparations, but they showed poor spatial and temporal coordination over even short distances (≤1 mm rostro-caudal axis). It is not commonly thought that electrical rhythmicity in gastrointestinal smooth muscle is dependent upon the enteric nervous system. Here, we identified neurogenic patterns of electrical rhythmicity in smooth muscle of the proximal region of isolated mouse colon, which are dependent on synaptic transmission in the enteric nervous system. If the whole colon is studied in vitro, recordings can preserve novel neurogenic patterns of electrical rhythmicity in smooth muscle. NEW & NOTEWORTHY Previously, it has not often been thought that electrical rhythmicity in smooth muscle of the gastrointestinal tract is dependent upon the enteric nervous system. We identified patterns of electrical rhythmicity in smooth muscle of the mouse proximal colon that were abolished by hexamethonium and involved the temporal synchronization of smooth muscle membrane potential over large spatial fields. We reveal different patterns of electrical rhythmicity in colonic smooth muscle that are dependent on the ENS.

Download Full-text

Localisation and activation of the neurokinin 1 receptor in the enteric nervous system of the mouse distal colon

Cell and Tissue Research ◽

10.1007/s00441-014-1822-z ◽

2014 ◽

Vol 356 (2) ◽

pp. 319-332 ◽

Cited By ~ 8

Author(s):

Juan-Carlos Pelayo ◽

Nicholas A. Veldhuis ◽

Emily M. Eriksson ◽

Nigel W. Bunnett ◽

Daniel P. Poole

Keyword(s):

Nervous System ◽

Enteric Nervous System ◽

Distal Colon ◽

Neurokinin 1 Receptor ◽

Neurokinin 1

Download Full-text

Somatostatin receptor subtype 2 mediates somatostatin inhibition of ion secretion in rat distal colon

Gastroenterology ◽

10.1053/gast.1996.v111.pm8690197 ◽

1996 ◽

Vol 111 (2) ◽

pp. 325-333 ◽

Cited By ~ 45

Author(s):

G Warhurst ◽

NB Higgs ◽

H Fakhoury ◽

AC Warhurst ◽

J Garde ◽

...

Keyword(s):

Somatostatin Receptor ◽

Distal Colon ◽

Receptor Subtype ◽

Ion Secretion ◽

Rat Distal Colon ◽

Somatostatin Receptor Subtype 2

Download Full-text

Macromolecular transport across the rabbit proximal and distal colon

Gut ◽

10.1136/gut.44.2.218 ◽

1999 ◽

Vol 44 (2) ◽

pp. 218-225 ◽

Cited By ~ 12

Author(s):

J A Hardin ◽

M H Kimm ◽

M Wirasinghe ◽

D G Gall

Keyword(s):

Nervous System ◽

Small Intestine ◽

Distal Colon ◽

Distal Segment ◽

Proximal Colon ◽

Colonic Epithelium ◽

Colonic Tissue ◽

Ussing Chambers ◽

Macromolecular Transport ◽

Energy Dependent

BackgroundAlthough many studies have investigated macromolecular uptake in the stomach and small intestine, little is known about macromolecular uptake in the colon.AimsTo investigate the mechanisms involved in the transport of large antigenically intact macromolecules across the proximal and distal colonic epithelium in the rabbit.MethodsThe mucosal to serosal movement of bovine serum albumin (BSA) was examined in modified Ussing chambers under short circuited conditions. The mucosal surface was exposed to varying concentrations of BSA, and after a 50 minute equilibration period, the mucosal to serosal flux of immunologically intact BSA was determined by ELISA. Total BSA flux was determined by the transport of radiolabelled 125I-BSA.ResultsIntact BSA transport in proximal and distal colonic tissue showed saturable kinetics. Intact BSA transport in the proximal and distal segment was 7% and 2% of the total 125I-BSA flux respectively. Immunologically intact BSA transport in the distal segment was significantly less than that in the proximal segment. Intact BSA transport in the proximal colon was significantly reduced following treatment with sodium fluoride, colchicine, and tetrodotoxin. Cholinergic blockade had no effect on the uptake of intact BSA.ConclusionThe findings indicate that the transport of intact macromolecules across the proximal and distal large intestine is a saturable process. Further, intact BSA transport in the proximal colon is an energy dependent process that utilises microtubules and is regulated by the enteric nervous system.

Download Full-text