Pharmacologic action of Escherichia coli heat-stable (STa) enterotoxin

Knoop, Floyd C.; Owens, M.J.

doi:10.1016/1056-8719(92)90049-7

Cited by 8 publications

(6 citation statements)

References 33 publications

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“…The numerical methods are applied to find conformations of the analog STh(6-19) of the peptide enterotoxin STh produced by E. coli in humans [20].…”

Section: Protocols and Numerical Resultsmentioning

confidence: 99%

Applications of weighting and chirality strategies for distance geometry algorithms to an enterotoxin peptide analog

et al. 1994

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Significant improvements are made to a recent algorithm that finds molecular conformations using distance geometry on nuclear magnetic resonance data. Weighting factors for the nearest approximation of the distance matrix to a data matrix are allowed to vary between iterations of the algorithm. These changes are proportional to the error of the distance between atoms in the configuration and the nuclear magnetic resonance data bounds. The weight changes increase the rate of convergence by an order of magnitude. Penalty functions are proposed to ensure the correct chirality. Numerical results for these modifications and subsequent energy calculations using CHARMm are given for an analog of the heat stable (ST) enterotoxin peptide STh produced by E. coliin humans.1. I n t r o d u c t i o n a n d b a c k g r o u n d Distance geometry is one method used to determine the conformation of molecules from nuclear magnetic resonance ( N M R ) data and other chemical information. A review of chemical distance geometry by G. Crippen m a y be found in ref. [1]. One m a y view distance geometry as a means of sampling the space of conformations consistent with the distance constraints, or as a means of generating chemically-reasonable structures (in terms of b o n d lengths and valence angles) for refinement by energy calculations. Distance geometry has made significant contributions to both the general determination of molecular conformation [2] and pharmaceutical design [3,4].Our distance geometry algorithms use the following notation and ideas. The chemical and N M R constraints yield a D a t a Box defined by upper, uij, and lower, l/j, bounds so that the distance, d/j between a t o m i and a t o m j in a molecule with n atoms should satisfy © J.C. Baltzer AG, Science Publishers

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“…The numerical methods are applied to find conformations of the analog STh(6-19) of the peptide enterotoxin STh produced by E. coli in humans [20].…”

Section: Protocols and Numerical Resultsmentioning

confidence: 99%

Applications of weighting and chirality strategies for distance geometry algorithms to an enterotoxin peptide analog

et al. 1994

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“…The discrepancy in the results may be due to differences in the sensitivities of the animals. Literature suggests that heat-stable and heat-labile E. coli enterotoxin and cholera toxin stimulate the mucosal cells of the small intestine through enzymic actions without tissue damage (Kaper et al, 1995;Knoop & Owens, 1992;Spangler, 1992). This appears to be the first study demonstrating biological activity of culture supernatant of CDT + and CDT 2 C. jejuni in the suckling mouse model.…”

Section: Discussionmentioning

confidence: 99%

Differences in virulence attributes between cytolethal distending toxin positive and negative Campylobacter jejuni strains

Jain

Prasad

Sinha

et al. 2008

Journal of Medical Microbiology

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Campylobacter jejuni is a common gastrointestinal bacterial pathogen. Although cytolethal distending toxin (CDT) is proposed to be an important virulence determinant of this pathogen, how CDT + and CDT " strains differ in their biological properties remains largely unknown. Mice inoculated with supernatant containing CDT activity had moderate to severe pathology in different parts of their gastrointestinal tract, with the colon being the major target. Mice inoculated with supernatant lacking CDT activity showed no significant pathology in the gastrointestinal tract. The results demonstrate that CDT + C. jejuni strains adhere to and invade epithelial cells more efficiently than CDT " strains. CDT is responsible for intestinal pathology and the colon is the major target.

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“…Additionally, regulation of intracellular Ca 2ϩ by cGMP has been described in several cell systems, including vascular smooth muscle (35), platelets (36), and neurons (37). In intestinal cells, ST activation of GC-C mobilizes intracellular Ca 2ϩ by a cGMPdependent mechanism (38,39). Further, ST and 8-br-cGMP induce Ca 2ϩ influx through CNG channels in colon (40).…”

Section: Resultsmentioning

confidence: 99%

Bacterial enterotoxins are associated with resistance to colon cancer

Pitari

Zingman

Hodgson

et al. 2003

Proc. Natl. Acad. Sci. U.S.A.

137

220

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One half million patients suffer from colorectal cancer in industrialized nations, yet this disease exhibits a low incidence in underdeveloped countries. This geographic imbalance suggests an environmental contribution to the resistance of endemic populations to intestinal neoplasia. A common epidemiological characteristic of these colon cancer-spared regions is the prevalence of enterotoxigenic bacteria associated with diarrheal disease. Here, a bacterial heat-stable enterotoxin was demonstrated to suppress colon cancer cell proliferation by a guanylyl cyclase C-mediated signaling cascade. The heat-stable enterotoxin suppressed proliferation by increasing intracellular cGMP, an effect mimicked by the cellpermeant analog 8-br-cGMP. The antiproliferative effects of the enterotoxin and 8-br-cGMP were reversed by L-cis-diltiazem, a cyclic nucleotide-gated channel inhibitor, as well as by removal of extracellular Ca 2؉ , or chelation of intracellular Ca 2؉ . In fact, both the enterotoxin and 8-br-cGMP induced an L-cis-diltiazem-sensitive conductance, promoting Ca 2؉ influx and inhibition of DNA synthesis in colon cancer cells. Induction of this previously unrecognized antiproliferative signaling pathway by bacterial enterotoxin could contribute to the resistance of endemic populations to intestinal neoplasia, and offers a paradigm for targeted prevention and therapy of primary and metastatic colorectal cancer.

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Pharmacologic action of Escherichia coli heat-stable (STa) enterotoxin

Cited by 8 publications

References 33 publications

Applications of weighting and chirality strategies for distance geometry algorithms to an enterotoxin peptide analog

Applications of weighting and chirality strategies for distance geometry algorithms to an enterotoxin peptide analog

Differences in virulence attributes between cytolethal distending toxin positive and negative Campylobacter jejuni strains

Bacterial enterotoxins are associated with resistance to colon cancer

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