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Luminal Cholera Toxin Alters Motility in Isolated Guinea-Pig Jejunum via a Pathway Independent of 5-HT(3) Receptors.

Fung C, Ellis M, Bornstein JC - Front Neurosci (2010)

Bottom Line: Its effects on intestinal motor patterns are less well understood.Luminal CT also reduced the pressure threshold for saline distension evoked propulsive reflexes, an effect resistant to granisetron.In contrast, CT prevented the induction of segmenting contractions by luminal decanoic acid, so its effects on propulsive and segmenting contractile activity are distinctly different.

View Article: PubMed Central - PubMed

Affiliation: Department of Physiology, University of Melbourne Parkville, VIC, Australia.

ABSTRACT
Cholera toxin (CT) is well established to produce diarrhea by producing hyperactivity of the enteric neural circuits that regulate water and electrolyte secretion. Its effects on intestinal motor patterns are less well understood. We examined the effects of luminal CT on motor activity of guinea-pig jejunum in vitro. Segments of jejunum were cannulated at either end and mounted horizontally. Their contractile activity was video-imaged and the recordings were used to construct spatiotemporal maps of contractile activity with CT (1.25 or 12.5 μg/ml) in the lumen. Both concentrations of CT induced propulsive motor activity in jejunal segments. The effect of 1.25 μg/ml CT was markedly enhanced by co-incubation with granisetron (5-HT(3) antagonist, 1 μM), which prevents the hypersecretion induced by CT. The increased propulsive activity was not accompanied by increased segmentation and occurred very early after exposure to CT in the presence of granisetron. Luminal CT also reduced the pressure threshold for saline distension evoked propulsive reflexes, an effect resistant to granisetron. In contrast, CT prevented the induction of segmenting contractions by luminal decanoic acid, so its effects on propulsive and segmenting contractile activity are distinctly different. Thus, in addition to producing hypersecretion, CT excites propulsive motor activity with an entirely different time course and pharmacology, but inhibits nutrient-induced segmentation. This suggests that CT excites more than one enteric neural circuit and that propulsive and segmenting motor patterns are differentially regulated.

No MeSH data available.


Related in: MedlinePlus

Effects of luminal CT on the threshold pressure for saline distension to evoke persistent propulsive contractions. (A) Histograms comparing the thresholds prior to exposure (first threshold) with those measured after 85 min of exposure (second threshold) for the time control (black), CT (1.25 μg/ml, red) and CT (1.25 μg/ml) plus granisetron (1 μM, blue). (B) Curves showing the diameter changes produced by each pressure set prior to exposure and after 85 min of exposure. *P < 0.05.
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Figure 3: Effects of luminal CT on the threshold pressure for saline distension to evoke persistent propulsive contractions. (A) Histograms comparing the thresholds prior to exposure (first threshold) with those measured after 85 min of exposure (second threshold) for the time control (black), CT (1.25 μg/ml, red) and CT (1.25 μg/ml) plus granisetron (1 μM, blue). (B) Curves showing the diameter changes produced by each pressure set prior to exposure and after 85 min of exposure. *P < 0.05.

Mentions: To determine if CT alters responses to standard reflexes, we examined the threshold pressure required to evoke “persistent propulsive contractions” (Gwynne et al., 2004), i.e., peristaltic reflexes, before and after 85 min of exposure to CT or CT plus granisetron. The threshold pressure that evoked consistent propulsive contractions was significantly lower after exposure to CT or to CT plus granisetron (P < 0.05 in each case, Figure 3A). Granisetron did not alter the effect of CT. The threshold pressure was also lower after 85 min of saline alone, but this difference was not significant (P > 0.05), consistent with earlier findings that threshold pressure for saline distension does not vary over at least 120 min (Gwynne et al., 2004).


Luminal Cholera Toxin Alters Motility in Isolated Guinea-Pig Jejunum via a Pathway Independent of 5-HT(3) Receptors.

Fung C, Ellis M, Bornstein JC - Front Neurosci (2010)

Effects of luminal CT on the threshold pressure for saline distension to evoke persistent propulsive contractions. (A) Histograms comparing the thresholds prior to exposure (first threshold) with those measured after 85 min of exposure (second threshold) for the time control (black), CT (1.25 μg/ml, red) and CT (1.25 μg/ml) plus granisetron (1 μM, blue). (B) Curves showing the diameter changes produced by each pressure set prior to exposure and after 85 min of exposure. *P < 0.05.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2967348&req=5

Figure 3: Effects of luminal CT on the threshold pressure for saline distension to evoke persistent propulsive contractions. (A) Histograms comparing the thresholds prior to exposure (first threshold) with those measured after 85 min of exposure (second threshold) for the time control (black), CT (1.25 μg/ml, red) and CT (1.25 μg/ml) plus granisetron (1 μM, blue). (B) Curves showing the diameter changes produced by each pressure set prior to exposure and after 85 min of exposure. *P < 0.05.
Mentions: To determine if CT alters responses to standard reflexes, we examined the threshold pressure required to evoke “persistent propulsive contractions” (Gwynne et al., 2004), i.e., peristaltic reflexes, before and after 85 min of exposure to CT or CT plus granisetron. The threshold pressure that evoked consistent propulsive contractions was significantly lower after exposure to CT or to CT plus granisetron (P < 0.05 in each case, Figure 3A). Granisetron did not alter the effect of CT. The threshold pressure was also lower after 85 min of saline alone, but this difference was not significant (P > 0.05), consistent with earlier findings that threshold pressure for saline distension does not vary over at least 120 min (Gwynne et al., 2004).

Bottom Line: Its effects on intestinal motor patterns are less well understood.Luminal CT also reduced the pressure threshold for saline distension evoked propulsive reflexes, an effect resistant to granisetron.In contrast, CT prevented the induction of segmenting contractions by luminal decanoic acid, so its effects on propulsive and segmenting contractile activity are distinctly different.

View Article: PubMed Central - PubMed

Affiliation: Department of Physiology, University of Melbourne Parkville, VIC, Australia.

ABSTRACT
Cholera toxin (CT) is well established to produce diarrhea by producing hyperactivity of the enteric neural circuits that regulate water and electrolyte secretion. Its effects on intestinal motor patterns are less well understood. We examined the effects of luminal CT on motor activity of guinea-pig jejunum in vitro. Segments of jejunum were cannulated at either end and mounted horizontally. Their contractile activity was video-imaged and the recordings were used to construct spatiotemporal maps of contractile activity with CT (1.25 or 12.5 μg/ml) in the lumen. Both concentrations of CT induced propulsive motor activity in jejunal segments. The effect of 1.25 μg/ml CT was markedly enhanced by co-incubation with granisetron (5-HT(3) antagonist, 1 μM), which prevents the hypersecretion induced by CT. The increased propulsive activity was not accompanied by increased segmentation and occurred very early after exposure to CT in the presence of granisetron. Luminal CT also reduced the pressure threshold for saline distension evoked propulsive reflexes, an effect resistant to granisetron. In contrast, CT prevented the induction of segmenting contractions by luminal decanoic acid, so its effects on propulsive and segmenting contractile activity are distinctly different. Thus, in addition to producing hypersecretion, CT excites propulsive motor activity with an entirely different time course and pharmacology, but inhibits nutrient-induced segmentation. This suggests that CT excites more than one enteric neural circuit and that propulsive and segmenting motor patterns are differentially regulated.

No MeSH data available.


Related in: MedlinePlus