The Aging Colon: The Role of Enteric Neurodegeneration in Constipation

Wiskur, Brandt; Meerveld, Beverley Greenwood‐Van

doi:10.1007/s11894-010-0139-7

Cited by 66 publications

(53 citation statements)

References 35 publications

(34 reference statements)

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“…Recent evidence also demonstrates that many neurological disorders, such as Parkinson's disease, not only affect the central nervous system but also cause neurodegeneration within the ENS 25 26. In patients with this type of disorder, neuronal morphological abnormalities can even be detected in the submucous plexus.…”

Section: Discussionmentioning

confidence: 99%

“…Our study is likely to have a significant impact on the field of gastroenterology, as it provides a novel tool to further the understanding of ENS abnormalities in either inflammatory or functional or even neurological disorder-related intestinal diseases, especially in those with unknown aetiology 25 26 34–40. This tool will also help to identify new pharmacological targets for the treatment of these pathologies.…”

Section: Discussionmentioning

confidence: 99%

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Nerve activity recordings in routine human intestinal biopsies

Cirillo

Tack

Berghe

2012

Gut

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Nerve activity recordings in routine human intestinal biopsies

Cirillo

Tack

Berghe

2012

Gut

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“…Simple bulking laxatives or stool softeners are usually effective and may need to be continued long-term. 7,8 Iron deficiency anaemia This topic will be discussed elsewhere in detail, so our comments are limited to some specific issues relevant to the older patient. Iron deficiency is the most common cause of anaemia worldwide and could be the first indicator of a more serious underlying condition.…”

Section: Constipationmentioning

confidence: 99%

Gastroenterology in the elderly

Mathialagan

Hariraj

2015

Medicine

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“…A 3 μmol/L concentration of granisetron was chosen for the present investigation based on dose-response curves previously obtained[9]. Moreover, because constipation has been ascribed to abnormalities of various contractile activities of the colon[16-19], parallel in vitro studies on isolated colon preparations were performed to evaluate (1) the neurogenic contractile responses to electrical field stimulation indicative of cholinergic and non-cholinergic transmitter release from enteric neurons[20,21] in the absence and in the presence of the muscarinic antagonist atropine as well as the nitric oxide synthase inhibitor L-NNA; and (2) the myogenic contractile response to ACh, one of the major contractile neurotransmitters at the gastrointestinal level in the absence and in the presence of L-NNA.…”

Section: Introductionmentioning

confidence: 99%

Carbon monoxide contributes to the constipating effects of granisetron in rat colon

Nacci¹,

Fanelli²,

Potenza³

et al. 2016

WJG

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AIMTo investigate the mechanisms underlying the potential contribution of the heme oxygenase/carbon monoxide (HO/CO) pathway in the constipating effects of granisetron.METHODSFor in vivo studies, gastrointestinal motility was evaluated in male rats acutely treated with granisetron [25, 50, 75 μg/kg/subcutaneous (sc)], zinc protoporphyrin IX [ZnPPIX, 50 μg/kg/intraperitoneal (ip)] and hemin (50 μmol/L/kg/ip), alone or in combination. For in vitro studies, the contractile neurogenic response to electrical field stimulation (EFS, 3, 5, 10 Hz, 14 V, 1 ms, pulse trains lasting 10 s), as well as the contractile myogenic response to acetylcholine (ACh, 0.1-100 μmol/L) were evaluated on colon specimens incubated with granisetron (3 μmol/L, 15 min), ZnPPIX (10 μmol/L, 60 min) or CO-releasing molecule-3 (CORM-3, 100, 200, 400 μmol/L) alone or in combination. These experiments were performed under co-treatment with or without atropine (3 μmol/L, a muscarinic receptor antagonist) or NG-nitro-L-Arginine (L-NNA, 100 μmol/L, a nitric oxide synthase inhibitor).RESULTSAdministration of granisetron (50, 75 μg/kg) in vivo significantly increased the time to first defecation (P = 0.045 vs vehicle-treated rats), clearly suggesting a constipating effect of this drug. Although administration of ZnPPIX or hemin alone had no effect on this gastrointestinal motility parameter, ZnPPIX co-administered with granisetron abolished the granisetron-induced constipation. On the other hand, co-administration of hemin and granisetron did not modify the increased constipation observed under granisetron alone. When administered in vitro, granisetron alone (3 μmol/L) did not significantly modify the colon’s contractile response to either EFS or ACh. Incubation with ZnPPIX alone (10 μmol/L) significantly reduced the colon’s contractile response to EFS (P = 0.016) but had no effect on contractile response to ACh. Co-administration of ZnPPIX and atropine (3 μmol/L) abolished the ZnPPIX-mediated decrease in contractile response to EFS. Conversely, incubation with CORM-3 (400 μmol/L) alone increased both the contractile response to EFS at 10 Hz (10 Hz: 71.02 ± 19.16 vs 116.25 ± 53.70, P = 0.01) and the contractile response to ACh (100 μmol/L) (P = 0.012). Co-administration of atropine abolished the CORM-3-mediated effects on the EFS-mediated response. When granisetron was co-incubated in vitro with ZnPPIX, the ZnPPIX-mediated decrease in colon contractile response to EFS was lost. On the other hand, co-incubation of granisetron and CORM-3 (400 μmol/L) further increased the colon’s contractile response to EFS (at 5 Hz: P = 0.007; at 10 Hz: P = 0.001) and to ACh (ACh 10 μmol/L: P = 0.001; ACh 100 μmol/L: P = 0.001) elicited by CORM-3 alone. L-NNA co-administered with granisetron and CORM-3 abolished the potentiating effect of CORM-3 on granisetron on both the EFS-induced and ACh-induced contractile response.CONCLUSIONTaken together, findings from in vivo and in vitro studies suggest that the HO/CO pathway is involved in the constipating effects of granisetron.

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The Aging Colon: The Role of Enteric Neurodegeneration in Constipation

Cited by 66 publications

References 35 publications

Nerve activity recordings in routine human intestinal biopsies

Nerve activity recordings in routine human intestinal biopsies

Gastroenterology in the elderly

Carbon monoxide contributes to the constipating effects of granisetron in rat colon

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