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Cholera toxin induc...
Cholera toxin induces sustained hyperexcitability in submucosal secretomotor neurons in guinea pig jejunum.
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Gwynne, Rachel M (author)
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Ellis, Melina (author)
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- Sjövall, Henrik, 1954 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för invärtesmedicin,Institute of Medicine, Department of Internal Medicine
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Bornstein, Joel C (author)
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(creator_code:org_t)
- Elsevier BV, 2009
- 2009
- English.
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In: Gastroenterology. - : Elsevier BV. - 1528-0012 .- 0016-5085. ; 136:1
- Related links:
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https://gup.ub.gu.se...
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https://doi.org/10.1...
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Abstract
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- BACKGROUND & AIMS: Neural mechanisms underlying cholera toxin (CT)-induced intestinal hypersecretion remain unclear. We investigated long-term excitability changes in vasoactive intestinal peptide (VIP) and neuropeptide Y (NPY) secretomotor neurons after prolonged luminal exposure to CT. METHODS: Isolated segments of guinea pig jejunum were incubated with saline or CT +/- neurotransmitter antagonist in the lumen; the submucosal plexus was then dissected clear, circumferentially adjacent to intact mucosa. Synaptic inputs and firing properties of S neurons in ganglia next to the mucosa in control saline were studied using intracellular recording. Neurons were processed for VIP and NPY immunoreactivity. RESULTS: Thirty S neurons (20 VIP(+), 7 NPY(+), 3 VIP(-)/NPY(-)) from CT-treated preparations and 27 control S neurons (19 VIP(+), 4 NPY(+), 4 VIP(-)/NPY(-)) in ganglia adjacent to intact mucosa were analyzed. VIP(+) and NPY(+) neurons in CT-treated preparations fired significantly more action potentials and for longer periods during injected depolarizing current pulses (50-350 pA) than control neurons. Addition of tetrodotoxin, hexamethonium, granisetron, or the neurokinin-1 (NK1) antagonist SR140333 during the CT incubation blocked CT-induced effects in both neuron types. The NK3 antagonist SR142801 blocked CT-induced effects in NPY(+) neurons and reduced the number of action potentials in VIP(+) neurons. Synaptic activity was unaffected by CT. CONCLUSIONS: CT induces specific and sustained hyperexcitability of secretomotor neurons in enteric pathways. CT acts in the mucosa. Its effect is neurally mediated and depends on 5-hydroxytryptamine-3, nicotinic, and NK1 receptors. This system represents a unique model to understand the neural mechanisms of action of CT and to identify therapeutic targets.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Gastroenterologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Gastroenterology and Hepatology (hsv//eng)
Keyword
- Cholera Toxin
- pharmacology
- Guinea Pigs
- Jejunum
- drug effects
- innervation
- Male
- Neuropeptide Y
- secretion
- Receptors
- Serotonin
- 5-HT3
- Submucous Plexus
- physiology
- Synaptic Potentials
- Vasoactive Intestinal Peptide
Publication and Content Type
- ref (subject category)
- art (subject category)
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