Chloride secretion

Opiates and various derivatives are commonly used to treat diarrhea, partly because they inhibit electrolyte secretion (Suzuki et al., 2000 Tumberg, 1983). Other phytochemicals counter the secretory responses to cholera toxin (Oi et al., 2002). An example would be the decreased chloride secretion caused by proanthocyanide and the ability to inhibit the secretory diarrhea caused by cholera toxin, but only if administered first (Hor et al., 1995). In the light of the co-transport of water and electrolytes by carriers of glucose... 

HOR M, RIMPLER H, HEINRICH M. (1995) Inhibition of intestinal chloride secretion by proanthocyanidins from Guazuma iilmifolia. Planta Med. 61 208-12. 

O In CF, the cystic fibrosis transmembrane regulator (CFTR) chloride channel is dysfunctional and usually results in decreased chloride secretion and increased sodium absorption, leading to altered viscosity of fluid excreted by the exocrine glands and mucosal obstruction. 

Table 1 Factors Modulating Chloride Secretion in the Cornea... 

UB Kompella, KJ Kim, VHL Lee. (1992). Paracellular permeability of a chloride secreting epithelium. Proc Int Symp Controlled Release 19 425-426. 

Fig. 11.4. Model for cholinergic signalling in the intestinal mucosa, providing a possible rationale for AChE secretion by parasitic nematodes. ACh released from enteric cholinergic motor neurons stimulates chloride secretion, mucus secretion and Paneth cell exocytosis through muscarinic receptors. Secretory responses may be modulated by mast cell mediators, either directly or via the induction of neural reflex programmes. The role of muscarinic receptor-positive cells in the lamina propria of rats infected with N. brasiliensis is undetermined, as are potential mechanisms of trans-epithelial transport of the enzymes. Adapted from Cooke (1984).

Water-soluble methylglyoxal adenine derivative 11 has recently been reported as a potentiator of wild-type and F508del-CFTR mutations in several cell lines [55]. Ex vivo addition of 11 to cftr mice colonic epithelium induced a dose-dependent elevation of chloride secretion with a measured EC50 of 175 + 1.1 pM. In vivo, in cftr+/ mice, addition of 11 in the presence of isoprenaline induced a dose-dependent salivary secretion with an EC50 of 7.1 + 1.1 pM whereas no effect of isoprenaline and 11 was observed on the salivary secretion of cftr mice. 

Cryptosporidium all ages/children in developing areas/immunocompromised adults/outbreaks in developed areas 7-10 days (range 5-28 days) intermittent and scant to continuous and watery prostaglandins —> cAMP-mediated apical chloride secretion and inhibition of electroneutral sodium chloride and water absorption release of IL-1, IL-8 and TNF-a... 

Although infection with C. parvum is considered predominantly secretory, histopathologic studies have revealed varying degrees of villous atrophy and infiltration of inflammatory cells beneath the epithelial mucosa [85, 86], Prostaglandins, which are known to induce cAMP-mediated apical chloride secretion and inhibit electroneutral sodium chloride and water absorption in enterocytes, have been demonstrated to be elevated in a porcine model of cryptosporidiosis [87], Inflammatory cytokines such as IL-1, IL-8 and TNF-a are induced in intestinal epithelial cell lines infected with Cryptosporidium and in animal models of cryptosporidiosis and have been postulated to play a role in pathogenesis [88, 89], Expression of TNF-a and IL-1 mRNA in the majority of jejunal biopsies of adult volunteers after experimental infection were also observed, although this did not correlate with the enteric symptoms [90]. 

Silva, P., F.H. Epstein, and R.J. Solomon. 1992. The effect of mercury on chloride secretion in the shark (,Squalus acanthias) rectal gland. Comp. Biochem. Physiol. 103C 569-575. 

Cozens AL, Yezzi MJ, Kunzelmann K, Ohrui T, Chin L, Eng K, Finkbeiner KE, Widdicombe JH, Gruenert DC (1994) CFTR expression and chloride secretion in polarized immortal human bronchial epithelial cells. Am J Respir Cell Mol Biol 10(1 ) 38—47. 

Shen, B. Q., R. A. Barthelson, W. Skach, D. C. Gruenert, E. Sigal, R. J. Mrsny, and J. H. Widdicombe. 1993. Mechanism of inhibition of cAMP-dependent epithelial chloride secretion by phorbol esters. J Biol Chem 268(25) 19070-5. 

Vibrio cholera exotoxin ADP-ribosylates G O, leading to an increase in cAMP and subsequently chloride secretion bom intestinal mucosal cells, causing the diarrhea of cholera. 

Chloride channel activator Lubiprostone, prostanoic acid derivative, stimulates chloride secretion into intestine, increasing fluid content... 

Reshkin SJ, Guerra L, Bagorda A, Debellis L, Cardone R, Li AH, Jacobson KA, Casavola V (2000) Activation of A adenosine receptor induces calcium entry and chloride secretion in A6 cells. J Membr Biol 178(2) 103-113... 

Sousa M, Ousingsawat J, Seitz R, Puntheeranurak S, Regalado A, Schmidt A, Grego T, Jansakul C, Amaral MD, Schreiber R, Kunzelmann K. 2007. An extract from the medicinal plant Phyllanthus acidus and its isolated compounds induce airway chloride secretion A potential treatment for cystic fibrosis. Mol Pharmacol 71 366-376. 

Rhubarb is a laxative, primarily owing to its influence on the motility of the colon, inhibiting stationary and stimulating propulsive contractions. This results in an accelerated intestinal passage and, because of the active chloride secretion, an increase in the water and electrolyte content of stool. 

Most studies of the local actions of opioids on the intestinal mucosa have utilized muscle-stripped sheets of ileal mucosa with attached submucosa mounted in Ussing flux chambers. Peptidase-resistant enkephalin derivatives such as DPDPE decrease short-circuit current, an electrical measure of active transepithelial ion transport, across isolated mucosal sheets from the guinea pig ileum [46,127,128], rabbit ileum [129-131], mouse jejunum [132], and pig distal jejunum/ileum [133]. This effect, which occurs after the application of opioid agonists to the serosal aspect of epithelial sheets, is due to an increase in electroneutral salt absorption and a decrease in electrogenic chloride secretion [46,132,133], In contrast to enkephalin derivatives, opiate alkaloids have limited effects on active transepithelial transport of ions [69]. Pretreat-... 

Induces active chloride secretion in Caco-2 cells [122]... 

Four general pathophysiologic mechanisms disrupt water and electrolyte balance, leading to diarrhea. These four mechanisms are the basis of diagnosis and therapy. They are (1) a change in active ion transport by either decreased sodium absorption or increased chloride secretion (2) a change in intestinal motility (3) an increase in luminal osmolarity and (4) an increase in tissue hydrostatic pressure. These mechanisms have been related to four broad clinical diarrheal groups secretory, osmotic, exudative, and altered intestinal transit. 

Vajanaphanich, M., Schultz, C., Rudolf, M.T., Wasserman, M., Enyedi, P., Craxton, A., Shears, S.B., Tsien, R.Y., Barrett, K.E. and Traynor-Kaplan, A., 1994, Long-term uncoupling of chloride secretion from intracellular calcium levels by Ins(3,4,5,6)P4. Nature 371 711-714. 

Rudolf, M.T., Dinkel, C., Traynor-Kaplan, A.E., and Schultz, C., 2003, Antagonists of myo-inositol 3,4,5,6-tetrakisphosphate allow repeated epithelial chloride secretion. Bioorg. Med. Chem. 11 3315-3329. 

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