» Articles » PMID: 7587800

Phorbol Myristate Acetate Ex Vivo Model of Enhanced Colonic Epithelial Permeability. Reactive Oxygen Metabolite and Protease Independence

Overview
Journal Dig Dis Sci
Specialty Gastroenterology
Date 1995 Oct 1
PMID 7587800
Citations 3
Authors
Affiliations
Soon will be listed here.
Abstract

The initiating mechanisms involved in colonic injury are currently unknown. The goal of the current study was to examine the role of the inflammatory mediators reactive oxygen metabolites and proteases in an ex vivo model of selective epithelial permeability. Rats were prepared with exteriorized colonic chambers to which the protein kinase C (PKC) activator phorbol myristate acetate (PMA) was added in doses ranging from 5 to 800 micrograms. PMA caused a dose-dependent transient increase in epithelial permeability, but had no significant effect on microvascular permeability. There was no accumulation of neutrophils and no apparent histological changes. PMA acts via a PKC-dependent mechanism, as assessed using the PKC-inactive phorbol analog 4 alpha-phorbol didecanoate, and the response is tachyphylactic. The mechanism is independent of reactive oxygen metabolites and proteases, as shown by the lack of effect of the free radical scavengers superoxide dismutase and catalase and the general serine protease inhibitor soybean trypsin inhibitor. The classic inflammatory process does not appear to be involved in the PMA-induced epithelial permeability changes. This finding suggests that noninflammatory mechanisms may regulate the increased epithelial permeability induced by PMA. Further study to elucidate these mechanisms is of importance for understanding both normal gastrointestinal physiology and initiation of pathology.

Citing Articles

Phorbol 12-Myristate 13-Acetate-Induced Changes in Chicken Enterocytes.

Rath N, Gupta A, Liyanage R, Lay Jr J Proteomics Insights. 2019; 10:1178641819840369.

PMID: 31019367 PMC: 6463336. DOI: 10.1177/1178641819840369.


Phorbol ester treatment increases paracellular permeability across IEC-18 gastrointestinal epithelium in vitro.

Marano C, Garulacan L, Ginanni N, Mullin J Dig Dis Sci. 2001; 46(7):1490-9.

PMID: 11478501 DOI: 10.1023/a:1010696005958.


Pentobarbital affects transepithelial electrophysiological parameters regulated by protein kinase C in rat distal colon.

Simons R, Laughlin K, Kampherstein J, Desai D, Shurina R, Mullin J Dig Dis Sci. 1998; 43(3):632-40.

PMID: 9539661 DOI: 10.1023/a:1018883712805.

References
1.
Onderdonk A, Bartlett J . Bacteriological studies of experimental ulcerative colitis. Am J Clin Nutr. 1979; 32(1):258-65. DOI: 10.1093/ajcn/32.1.258. View

2.
Fretland D, Levin S, Tsai B, Djuric S, Widomski D, Zemaitis J . The effect of leukotriene-B4 receptor antagonist, SC-41930, on acetic acid-induced colonic inflammation. Agents Actions. 1989; 27(3-4):395-7. DOI: 10.1007/BF01972832. View

3.
English D, Roloff J, Lukens J . Chemotactic factor enhancement of superoxide release from fluoride and phorbol myristate acetate stimulated neutrophils. Blood. 1981; 58(1):129-34. View

4.
Vilaseca J, Salas A, Guarner F, Rodriguez R, Malagelada J . Participation of thromboxane and other eicosanoid synthesis in the course of experimental inflammatory colitis. Gastroenterology. 1990; 98(2):269-77. DOI: 10.1016/0016-5085(90)90814-h. View

5.
Yamamoto S, Kiyoto I, Aizu E, Nakadate T, Hosoda Y, Kato R . Differential inhibition by staurosporine, a potent protein kinase C inhibitor, of 12-O-tetradecanoylphorbol-13-acetate-caused skin tumor promotion, epidermal ornithine decarboxylase induction, hyperplasia and inflammation. Carcinogenesis. 1989; 10(7):1315-22. DOI: 10.1093/carcin/10.7.1315. View