Comprehensive Physiology Wiley Online Library

Alterations of small intestine motility by bacteria and their enterotoxins

Full Article on Wiley Online Library



Abstract

The sections in this article are:

1 Historical Background and Animal Model
2 Migrating Action‐Potential Complex (Mapc)
2.1 Cholera toxin
2.2 Choleragen and Choleragenoid
2.3 Historical Background of MAPC
2.4 Association of MAPC With Prostaglandins
2.5 Relationship of Enteric Nervous System With MAPC
2.6 Mapc In Vitro
2.7 Other Substances that Stimulate MAPC
2.8 Control Mechanisms of MAPC
2.9 Questions for the Future
3 Repetitive Bursts of Action Potentials
3.1 Invasive Escherichia coli
3.2 Shigella dysenteriae 1 and Purified Enterotoxin From Strain 60R
3.3 Clostridium perfringens A Enterotoxin
3.4 Clostridium difficile
3.5 Heat‐Stable Toxins From Escherichia coli
3.6 Campylobacter jejuni
3.7 Summary
4 Bacterial Overgrowth of Small Intestine
4.1 Mechanisms of Diarrhea
4.2 Questions for the Future
5 Summary
Figure 1. Figure 1.

Schematic of 12‐cm distal ileal loop model. Four monopolar silver‐silver chloride electrodes (No. 1–4) are placed 2.5 cm apart on ileal loop. Small catheter is inserted proximally for administration of test material. Larger catheters are inserted distally for outflow of luminal contents from proximal ileum and from loop.

Adapted from Mathias et al.
Figure 2. Figure 2.

Control tracing from distal ileal segment. Electrode placement is illustrated on the left. Time and sensitivity calibrations are also shown. Slow‐wave rhythm is illustrated on all four electrode sites. There is brief action potential activity on lead three; it is also shown in enlarged enclosure.

From Burns et al.
Figure 3. Figure 3.

Migrating action‐potential complex (MAPC). Electrode placement is illustrated on the left. Time and sensitivity calibrations are also shown. Slope of line as compared with vertical reference line represents propagation velocity of MAPC. Propagation velocity of this complex was 0.85 cm/s.

From Mathias et al.
Figure 4. Figure 4.

Onset time of migrating action‐potential complex (MAPC) activity for 8‐h recording period. Abscissa, mean number of MAPC/h. Solid bars, controls (saline); hatched bars, cholera‐infected loops. Results are expressed as mean ± SE.

From Mathias et al.
Figure 5. Figure 5.

Effect of cyclooxygenase inhibitors [aspirin (acetylsalicylic acid) and indomethacin] on propagation velocity of migrating action‐potential complex. Hatched bar, cholera‐infected loops; clear bar, cholera‐infected loops treated with aspirin; and dotted bar, cholera‐infected loops treated with indomethacin. Results are expressed as mean ± SE.

Figure 6. Figure 6.

Effect of cyclooxygenase inhibitors [aspirin (acetylsalicylic acid) and indomethacin] on fluid output from distal ileal catheter. Hatched bar, cholera‐infected loops; clear bar, cholera‐infected loops treated with aspirin; dotted bar, cholera‐infected loops treated with low‐dose indomethacin; and solid bar, cholera‐infected loops treated with high‐dose indomethacin. High‐dose indomethacin inhibited all migrating action‐potential complex activity. Results are expressed as mean ± SE.

Figure 7. Figure 7.

Effect of cyclooxygenase inhibitor, indomethacin, on prostaglandin F‐infused ileal loops and on cholera‐infected ileal loops. Results are from ileal loops in three rabbits exposed to prostaglandin F (left) and three rabbits exposed to cholera toxin (right), before and after treatment with indomethacin (2.0 mg/kg IV). Results are expressed as mean ± SE.

Figure 8. Figure 8.

Theoretical cascade and feedback control of cellular functions. Cascade involves interaction of protein kinases A, G, and C with inositol phospholipids, which results in the mobilization of calcium and formation of prostinoids. This schema was developed from platelet model but may be applicable for activities occurring at epithelial cell of small intestine.

From Nishizuka . Copyright 1984, by the American Association for the Advancement of Science
Figure 9. Figure 9.

Schematic of possible neural reflex arcs of enteric nervous system, which may provide an explanation for secretory‐motor events of cholera toxin‐induced disease (see Table ). Enlarged areas, enterocytes (left) and enterocytes with an enterochromaffin cell (right); small open circles, submucosal reflex arc; and small closed circles, intrinsic reflex arc involving myenteric plexus.

Figure 10. Figure 10.

Effects of specific neuroantagonists on migrating action‐potential complex (MAPC) activity. Results are from cholera‐infected loops after peak MAPC activity and are expressed as mean ± SE. Asterisk, P < 0.02 compared with choleragen.

Figure 11. Figure 11.

Effect of 6‐hydroxydopamine on activity front of migrating myoelectric complex (MMC). Electrode placement is illustrated on the left, and time and sensitivity calibrations are also indicated. Migrating action‐potential complexes (MAPC) are shown preceding activity front of MMC. Propagation velocity of MAPC (sloped line on the left) was 0.84 cm/s; propagation velocity of MMC (sloped line on the right) was 3.65 cm/min.

From Mathias et al.
Figure 12. Figure 12.

Migrating action‐potential complexes observed in rabbit colon secondary to deoxycholic acid. Electrode placement is shown schematically on the left: E1‐E4 are on ascending colonic loop and E5 is distal to loop. Strain gauge 1 (SG‐1) is located between E2 and E3. Respiration is indicated on bottom tracing, and time and sensitivity calibrations are also shown.

From Shiff et al.
Figure 13. Figure 13.

Repetitive bursts of action potentials (RBAP). Electrode placement is illustrated schematically on the left, and time and sensitivity calibrations are also shown. Action potential activity >1.5 s in duration, occurring over at least three successive slow waves on single recording site, is shown on electrode 1. RBAP activity may propagate short distances, as shown in this instance, but it usually does not.

Figure 14. Figure 14.

Effects of products from Clostridium difficile on myoelectric activity in rabbit ileum. Controls, saline; control media, brain‐heart broth; CDCF, C. difficile culture filtrate; HMW, high‐molecular‐weight fraction from C. difficile (>50,000 Mr); LMW, low‐molecular‐weight fraction from C. difficile (<50,000 Mr). Results are expressed as mean ± SE.

From Justus et al. . Copyright 1982 by The American Gastroenterological Association
Figure 15. Figure 15.

Effects of heat‐stable toxin (STa) from Escherichia coli. Stippled bars, repetitive bursts of action potentials (RBAP); solid bars, migrating action‐potential complexes (MAPC). mu, Mouse units; asterisk, P < 0.05. Results are expressed as mean ± SE.

From Mathias et al.
Figure 16. Figure 16.

Effects on repetitive bursts of action potential (RBAP) activity of STa inactivated by dithiothreitol. Stippled bars, RBAP; solid bars, migrating action‐potential complexes (MAPC). Results are of active STa (ST toxin); inactivated STa (inactivated toxin), and saline controls and are expressed as mean ± SE. Asterisk, P < 0.03.

From Mathias et al.
Figure 17. Figure 17.

Number of migrating action‐potential complexes (MAPC) per hour in control, self‐emptying blind loop rats (SEBL), self‐filling blind loop rats (SFBL), and SFBL rats treated with chloramphenicol (SFBL‐Chloro) in the experimental bacterial overgrowth syndrome. Results are expressed as mean ± SE. Double asterisk, P < 0.01 compared with SFBL rats.

From Justus et al.
Figure 18. Figure 18.

Repetitive bursts of action‐potential activity expressed as slow waves occupied by action potentials (% SW‐AP) in control rats, self‐emptying blind loop rats (SEBL), self‐filling blind loop rats (SFBL), and SFBL rats treated with chloramphenicol (SFBL‐Chloro) in experimental bacterial overgrowth syndrome. Open bar, sections proximal (afferent) to loop; stippled bar, sections distal (efferent) to loop; striped bar, blind loop itself. Results are expressed as mean ± SE. Asterisk, P < 0.05; double asterisk, P < 0.01 compared with SFBL rats.

From Justus et al.
Figure 19. Figure 19.

Number of migrating action‐potential complexes (MAPC) per hour in control rats, gnotobiotic rats, self‐filling blind loop rats (SFBL), and SFBL rats 2, 7, and 21 days after the loops were surgically removed. Results are expressed as mean ± SE. Asterisk, P < 0.05 compared with SFBL rats.

From Justus et al.
Figure 20. Figure 20.

Repetitive bursts of action potential activity expressed as slow waves occupied by action potentials (% SW‐AP) in afferent (open bars) and efferent (stippled bars) sections of the jejunum of control rats, gnotobiotic rats, self‐filling blind loop (SFBL) rats, and SFBL rats 2, 7, and 21 days after loops were surgically removed. Results are expressed as mean ± SE.

From Justus et al.


Figure 1.

Schematic of 12‐cm distal ileal loop model. Four monopolar silver‐silver chloride electrodes (No. 1–4) are placed 2.5 cm apart on ileal loop. Small catheter is inserted proximally for administration of test material. Larger catheters are inserted distally for outflow of luminal contents from proximal ileum and from loop.

Adapted from Mathias et al.


Figure 2.

Control tracing from distal ileal segment. Electrode placement is illustrated on the left. Time and sensitivity calibrations are also shown. Slow‐wave rhythm is illustrated on all four electrode sites. There is brief action potential activity on lead three; it is also shown in enlarged enclosure.

From Burns et al.


Figure 3.

Migrating action‐potential complex (MAPC). Electrode placement is illustrated on the left. Time and sensitivity calibrations are also shown. Slope of line as compared with vertical reference line represents propagation velocity of MAPC. Propagation velocity of this complex was 0.85 cm/s.

From Mathias et al.


Figure 4.

Onset time of migrating action‐potential complex (MAPC) activity for 8‐h recording period. Abscissa, mean number of MAPC/h. Solid bars, controls (saline); hatched bars, cholera‐infected loops. Results are expressed as mean ± SE.

From Mathias et al.


Figure 5.

Effect of cyclooxygenase inhibitors [aspirin (acetylsalicylic acid) and indomethacin] on propagation velocity of migrating action‐potential complex. Hatched bar, cholera‐infected loops; clear bar, cholera‐infected loops treated with aspirin; and dotted bar, cholera‐infected loops treated with indomethacin. Results are expressed as mean ± SE.



Figure 6.

Effect of cyclooxygenase inhibitors [aspirin (acetylsalicylic acid) and indomethacin] on fluid output from distal ileal catheter. Hatched bar, cholera‐infected loops; clear bar, cholera‐infected loops treated with aspirin; dotted bar, cholera‐infected loops treated with low‐dose indomethacin; and solid bar, cholera‐infected loops treated with high‐dose indomethacin. High‐dose indomethacin inhibited all migrating action‐potential complex activity. Results are expressed as mean ± SE.



Figure 7.

Effect of cyclooxygenase inhibitor, indomethacin, on prostaglandin F‐infused ileal loops and on cholera‐infected ileal loops. Results are from ileal loops in three rabbits exposed to prostaglandin F (left) and three rabbits exposed to cholera toxin (right), before and after treatment with indomethacin (2.0 mg/kg IV). Results are expressed as mean ± SE.



Figure 8.

Theoretical cascade and feedback control of cellular functions. Cascade involves interaction of protein kinases A, G, and C with inositol phospholipids, which results in the mobilization of calcium and formation of prostinoids. This schema was developed from platelet model but may be applicable for activities occurring at epithelial cell of small intestine.

From Nishizuka . Copyright 1984, by the American Association for the Advancement of Science


Figure 9.

Schematic of possible neural reflex arcs of enteric nervous system, which may provide an explanation for secretory‐motor events of cholera toxin‐induced disease (see Table ). Enlarged areas, enterocytes (left) and enterocytes with an enterochromaffin cell (right); small open circles, submucosal reflex arc; and small closed circles, intrinsic reflex arc involving myenteric plexus.



Figure 10.

Effects of specific neuroantagonists on migrating action‐potential complex (MAPC) activity. Results are from cholera‐infected loops after peak MAPC activity and are expressed as mean ± SE. Asterisk, P < 0.02 compared with choleragen.



Figure 11.

Effect of 6‐hydroxydopamine on activity front of migrating myoelectric complex (MMC). Electrode placement is illustrated on the left, and time and sensitivity calibrations are also indicated. Migrating action‐potential complexes (MAPC) are shown preceding activity front of MMC. Propagation velocity of MAPC (sloped line on the left) was 0.84 cm/s; propagation velocity of MMC (sloped line on the right) was 3.65 cm/min.

From Mathias et al.


Figure 12.

Migrating action‐potential complexes observed in rabbit colon secondary to deoxycholic acid. Electrode placement is shown schematically on the left: E1‐E4 are on ascending colonic loop and E5 is distal to loop. Strain gauge 1 (SG‐1) is located between E2 and E3. Respiration is indicated on bottom tracing, and time and sensitivity calibrations are also shown.

From Shiff et al.


Figure 13.

Repetitive bursts of action potentials (RBAP). Electrode placement is illustrated schematically on the left, and time and sensitivity calibrations are also shown. Action potential activity >1.5 s in duration, occurring over at least three successive slow waves on single recording site, is shown on electrode 1. RBAP activity may propagate short distances, as shown in this instance, but it usually does not.



Figure 14.

Effects of products from Clostridium difficile on myoelectric activity in rabbit ileum. Controls, saline; control media, brain‐heart broth; CDCF, C. difficile culture filtrate; HMW, high‐molecular‐weight fraction from C. difficile (>50,000 Mr); LMW, low‐molecular‐weight fraction from C. difficile (<50,000 Mr). Results are expressed as mean ± SE.

From Justus et al. . Copyright 1982 by The American Gastroenterological Association


Figure 15.

Effects of heat‐stable toxin (STa) from Escherichia coli. Stippled bars, repetitive bursts of action potentials (RBAP); solid bars, migrating action‐potential complexes (MAPC). mu, Mouse units; asterisk, P < 0.05. Results are expressed as mean ± SE.

From Mathias et al.


Figure 16.

Effects on repetitive bursts of action potential (RBAP) activity of STa inactivated by dithiothreitol. Stippled bars, RBAP; solid bars, migrating action‐potential complexes (MAPC). Results are of active STa (ST toxin); inactivated STa (inactivated toxin), and saline controls and are expressed as mean ± SE. Asterisk, P < 0.03.

From Mathias et al.


Figure 17.

Number of migrating action‐potential complexes (MAPC) per hour in control, self‐emptying blind loop rats (SEBL), self‐filling blind loop rats (SFBL), and SFBL rats treated with chloramphenicol (SFBL‐Chloro) in the experimental bacterial overgrowth syndrome. Results are expressed as mean ± SE. Double asterisk, P < 0.01 compared with SFBL rats.

From Justus et al.


Figure 18.

Repetitive bursts of action‐potential activity expressed as slow waves occupied by action potentials (% SW‐AP) in control rats, self‐emptying blind loop rats (SEBL), self‐filling blind loop rats (SFBL), and SFBL rats treated with chloramphenicol (SFBL‐Chloro) in experimental bacterial overgrowth syndrome. Open bar, sections proximal (afferent) to loop; stippled bar, sections distal (efferent) to loop; striped bar, blind loop itself. Results are expressed as mean ± SE. Asterisk, P < 0.05; double asterisk, P < 0.01 compared with SFBL rats.

From Justus et al.


Figure 19.

Number of migrating action‐potential complexes (MAPC) per hour in control rats, gnotobiotic rats, self‐filling blind loop rats (SFBL), and SFBL rats 2, 7, and 21 days after the loops were surgically removed. Results are expressed as mean ± SE. Asterisk, P < 0.05 compared with SFBL rats.

From Justus et al.


Figure 20.

Repetitive bursts of action potential activity expressed as slow waves occupied by action potentials (% SW‐AP) in afferent (open bars) and efferent (stippled bars) sections of the jejunum of control rats, gnotobiotic rats, self‐filling blind loop (SFBL) rats, and SFBL rats 2, 7, and 21 days after loops were surgically removed. Results are expressed as mean ± SE.

From Justus et al.
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John R. Mathias, Mary H. Clench. Alterations of small intestine motility by bacteria and their enterotoxins. Compr Physiol 2011, Supplement 16: Handbook of Physiology, The Gastrointestinal System, Motility and Circulation: 1153-1177. First published in print 1989. doi: 10.1002/cphy.cp060131