Prostaglandin Cholera

Diarrhea is a common problem that is usually self-limiting and of short duration. Increased accumulations of small intestinal and colonic contents are known to be responsible for producing diarrhea. The former may be caused by increased intestinal secretion which may be enterotoxin-induced, eg, cholera and E. col] or hormone and dmg-induced, eg, caffeine, prostaglandins, and laxatives decreased intestinal absorption because of decreased mucosal surface area, mucosal disease, eg, tropical spme, or osmotic deficiency, eg, disaccharidase or lactase deficiency and rapid transit of contents. An increased accumulation of colonic content may be linked to increased colonic secretion owing to hydroxy fatty acid or bile acids, and exudation, eg, inflammatory bowel disease or amebiasis decreased colonic absorption caused by decreased surface area, mucosal disease, and osmotic factors and rapid transit, eg, irritable bowel syndrome. 

Peterson JW, Ochoa LG Role of prostaglandins and cAMP in the secretory effects of cholera toxin. Science 1989 245 857-859. 

A notable finding was the defective transport of D-glucose, uridine, and two amino acid analogs (2-aminobutanoate and cycloleucine) in chick-embryo cells in which glycosylation of proteins was prevented by tunicamycin. Other membrane-associated processes, such as the enzymic activities of Na/K ATPase and adenylate cyclase, or the stimulation of adenylate cyclase by a prostaglandin and cholerae toxin, were not affected.546... 

There is another large class of receptors whose occupancy by an agonisf leads to inhibition of adenylate cyclase. These include the tt2 adrenergic receptors, receptors for acetylcholine, adenosine, prostaglandin E2 (Chapter 21), somatostatin, and some receptors for dopamine. Their responses are mediafed by inhibitory proteins Gj, which closely resemble Gg in their sizes, amino acid sequences, and heterotrimeric structures, but which inhibit adenylate cyclase when activated. A clear distinction between the Gg and Gj proteins is evident in the fact that Gg is irreversibly activated by the action of cholera toxin, while G loses its ability to respond to occupied receptors when modified by the action of Pertussis toxin (Box 11-A). A specialized heterotrimeric G protein known as transducin mediates the light-induced activation of a cyclic GMP phosphodiesterase in the retina " (see Chapter 23). Its a subunit is designated aj. The related gustducin is found in taste buds. ... 

Botella A, Vabre F, Fioramonti J et al 1993 In vivo inhibitory effect of lanreotide (BIM 23014), a new somatostatin analog, on prostaglandin- and cholera toxin-stimulated intestinal fluid in the rat. Peptides 14 297-301 Brzozowski T, Konturek S J, Sliwowski Z et al 1997 Role of L-arginine, a substrate for NO-synthase, in gastroprotection and ulcer healing. Journal of Gastroenterology 32 442-452... 

Fluid and electrolyte loss in cholera patients is closely related to elevated concentrations of cAMP, which can stimulate chloride secretion in intestinal epithelial cells (Field, 1971 Moss and Vaughan, 1988a). There is also evidence for the importance of other substances, such as prostaglandin E2 (PGE2) and 5-hydroxytryptamine (5-HT), in CT-induced secretion (Kaper et al., 1995). Nilsson et al. (1983) reported that 5-HT was released from enterochromaffin cells in the cat small intestine upon CT treatment. 5-HT could then stimulate PGE2 synthesis (Beubler etai, 1989) and activate the enteric nervous system (Ekiund et al., 1984). Cholera toxin also caused release of PGE2 into the lumen of intestinal loops in vitro (Peterson and Ochoa, 1989), via an effect on arachidonic acid formation (Peterson et al., 1990 Reit-meyer and Peterson, 1990). The contribution of these, and perhaps other, CT effects to the pathogenesis of cholera remains to be elucidated (Peterson etai, 1994). 

Beubler E, Kollar G, Soria A, et al. (1989) Involvement of 5-hydroxytryptamine, prostaglandin E2, and cyclic adenosine monophosphate in cholera toxin-induced fluid secretion in the small intestine of rat in vivo. In Gastroenter. 96 368-376. 

Peterson JW, Jackson CA, Reitmeyer JC (1990) Synthesis of prostaglandins in cholera toxin-treated Chinese hamster ovary cells. In Microb. Pathogen. 9 345-353. 

Iodide by an Xl-type mechanism inhibits both cAMP and the phospholipase G cascades (Figure 32.2). The inhibition of TSH, prostaglandin El (PGEl), cholera toxin and forskolin-activated cAMP cascade bears on Gs— adenylyl cyclase couple and on cAMP generation (Gochaux et al, 1987 Filetti and Rapoport, 1983 ... 

Bagley KC, Abdehvahab SF, Tuskan RG ct al. Cholera toxin indirectly activates human monocyte-derived dendritic cells in vitro through the production of soluble factors, including prostaglandin (2] and nitric oxide. Clin Vaccine Immunol 2006 13(1) 106-115. 

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