Nitric oxide counteracts 5-hydroxytryptamine- and cholera toxin-induced fluid secretion and enhances the effect of oral rehydration solution

Beubler, Eckhard; Schirgi‐Degen, Andrea

doi:10.1016/s0014-2999(97)85417-9

Cited by 21 publications

(17 citation statements)

References 17 publications

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“…Our data are consistent with previous results by Beubler and Schirgi-Degen (27) reporting that i.v. administration of L-NAME enhanced CT-induced ion secretion in rat ligated jejunal loops, whereas the NO precursor L-arginine inhibited it.…”

Section: No Regulates Enterocyte Ion Transportsupporting

confidence: 94%

“…The effects of NO in response to CT in Caco-2 cells resemble those observed with other secretagogues including prostaglandin E 2 , Escherichia coli heat-stable enterotoxin, and Clostridium difficile toxin A (27), and suggest that NO is able to down-regulate fluid secretion elicited by different secretagogues, including those acting through intracellular mechanisms other than cAMP. This may suggest that NO is released in response to cyclic nucleotide concentration.…”

Section: No Regulates Enterocyte Ion Transportmentioning

confidence: 58%

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Nitric Oxide Produced by the Enterocyte Is Involved in the Cellular Regulation of Ion Transport

et al. 2003

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The role of nitric oxide (NO) in the intestinal basal ion transport and under conditions of enterotoxin-induced ion secretion is controversial. Namely it is not clear whether NO enhances or counteracts intestinal ion secretion and whether the effects on transport result from a direct interaction with the enterocyte. The cell origin of NO is also unclear. We have tested the hypothesis that NO produced by the enterocyte directly regulates ion transport processes either in basal condition or in response to cholera toxin-induced secretion. Electrical variables reflecting transepithelial ion transport were measured in Caco-2 cell monolayers mounted in Ussing chambers exposed to the NO synthase inhibitor N-nitro-L-arginine methyl ester, in the presence or absence of cholera toxin. cAMP concentrations were also measured. NO release was determined by nitrite-nitrate concentration. NO synthase activities were assayed by Western blot analysis. N-nitro-L-arginine methyl ester had a secretory effect, as judged by increased basal short-circuit current and cAMP concentration. It also increased cholera toxin-induced electrical response and cAMP production. Either cholera toxin or the cAMP analog 8-bromo-cAMP induced a rapidly progressive and Ca 2ϩ -dependent increase in NO concentration, suggesting a homeostatic up-regulation of the constitutive form of NO synthase.Western blot analysis showed an increase in constitutive NO synthase enzyme isoform. These results indicate that the enterocyte regulates its own ion transport processes, either in basal condition or in the presence of active secretion, through the activation of a constitutive NO synthase-NO pathway, functioning as a braking force of cAMP-induced ion secretion. Intestinal water and electrolyte transepithelial transport is under a complex control by several agents including neurotransmitters, hormones, or paracrine agents (1). There is evidence that NO takes part in the intestinal ion transport processes with an effect that involves the enteric nervous system, the suppression of prostaglandin formation, and the opening of K ϩ channels (2, 3). NO is a gas with a half-life of less than 5 s, rapidly degrading to nitrite and nitrate in the presence of oxygen and water. NO is produced by a number of cells, including neuronal cells, and released in various organs. Being soluble in both water and lipids, it freely passes into adjacent target cells (2,4). NO is generated from L-arginine by a family of enzymes, NOS, whose activity can be stereospecifically inhibited by L-but not by D-arginine analogs (5). Two NOS are constantly active in the intestine and are termed cNOS. They include the neuronal NOS (NOS 1) and the endothelial NOS (NOS 3). Both are Ca 2ϩ /calmodulin-dependent, produce small amounts of NO in short burst, and are involved in several homeostatic processes. A third NOS form, which is Ca 2ϩ /calmodulin-independent, is activated by various signal molecules, including proinflammatory cytokines. This latter form, termed iNOS (NOS 2), requires at least 2 h to be act...

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Section: No Regulates Enterocyte Ion Transportsupporting

confidence: 94%

Section: No Regulates Enterocyte Ion Transportmentioning

confidence: 58%

Nitric Oxide Produced by the Enterocyte Is Involved in the Cellular Regulation of Ion Transport

et al. 2003

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“…Measurement of Na ± , Cl − , or 22 Na ± unidirectional efflux. The same operative procedure was used as stated above (3,7).…”

Section: Methodsmentioning

confidence: 99%

“…The same operative procedure was used as stated above (3,7). The loop was filled with 3 ml lactated Ringer's solution containing [ 14 C]inulin (for Na + and Cl − net flux) or containing 22 Na + (5 µCi) and 3 mg unlabeled inulin (for 22 Na + ion movement and loop volume determinations). A 0.15-ml liquid sample was taken at time 0, after which Ringer's solution was infused intravenously at 20 µl/kg/min for 15 min, followed by removal of a second 0.15-ml sample.…”

Section: Methodsmentioning

confidence: 99%

“…Samples (385 µl) were used for Na + and Cl − determination by Nova Analyzer (Nova Biomedical, Waltham, Massachusetts, USA). Samples (50 µl) were assayed for 22 Na + by gamma counting and for inulin by a standard method (12). We calculated Na + and Cl − net absorption by the formula V 0 C 0 -V X C X , in which V 0 and C 0 are the volume of fluid and concentration of Na + or Cl − at time 0, and V X and C X are the volume and Na + or Cl − concentration after drug or vehicle administration for 15 min.…”

Section: Methodsmentioning

confidence: 99%

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Compartmentalization of extracellular cGMP determines absorptive or secretory responses in the rat jejunum

Jin

Siragy²,

Guerrant³

et al. 1999

J. Clin. Invest.

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Angiotensin II (ANG II) regulates sodium and water transport across epithelial cells in the kidney and gastrointestinal tract (1-5). In the jejunum, low concentrations of ANG II stimulate sodium and water absorption while high concentrations inhibit absorption and/or stimulate secretion (3). We have recently demonstrated that ANG II stimulates absorption in the jejunum by an action at the AT 2 receptor involving the generation of guanosine cyclic 3′,5′-monophosphate (cGMP) (3,6,7).In this study, we hypothesized that ANG II increases jejunal sodium and water absorption by increasing the synthesis of nitric oxide (NO) and stimulating soluble guanylyl cyclase. However, since cGMP is thought to mediate secretory, not absorptive, responses in the gastrointestinal tract when particulate guanylyl cyclase (GC-C) is stimulated by the heat-stable enterotoxin of Escherichia coli (STa) or guanylin or uroguanylin (8, 9), we hypothesized that the sodium and water transport response, absorptive or secretory, is associated with a compartmentalized cGMP response via either soluble or particulate guanylyl cyclase. If so, STa would stimulate secretion by stimulating particulate guanylyl cyclase on the apical cell membrane of transporting epithelial cells. In contradistinction, nitric oxide would stimulate absorption via soluble guanylyl cyclase from the serosal side, and cGMP would be released predominantly across the basolateral membrane of epithelial cells into the interstitial space. We introduced both in situ loop and microdialysis techniques to test these hypotheses. MethodsAnimal preparation. Male Wistar rats weighing 200 ± 15 g were obtained from Harlan Bioproducts Inc. (Indianapolis, Indiana, USA). Rats were housed in a room with 12-h light-dark cycles and maintained on standard rat chow containing 0.28% NaCl or low-sodium chow containing 0.08% NaCl (BioServe Biotechnologies, Frenchtown, New Jersey, USA). Rats were fasted overnight before the study.Operative procedure. Rats (n = 8 in each group) were anesthetized with pentobarbital sodium 70 mg/kg intraperitoneally (Veterinary Laboratories, Inc., Lenexa, Kansas). The trachea and left jugular vein were cannulated. A venous cannula (PE 50) was connected to a Harvard 975 infusion pump (Harvard Apparatus Co., South Natick, Massachusetts, USA) through which lactated Ringer's solution (vehicle) and drugs were infused. A ventral midline celiotomy also was performed and the jejunum was prepared in two different ways as described below.Single-pass perfusion. These studies were performed according to previous publications (10, 11). An inlet cannula was placed just below the duodenal-jejunal flexure and the outlet cannula was 15 cm distal to the inlet cannula. The lumen just proximal and distal to the cannulated segment was tied off. To measure water transport, lactated Ringer's solution containing [ 14 C]inulin (15,000 dpm/ml; 2.2 µCi/mg specific activity; New England Nuclear, Boston, Massachusetts, USA) and phenol red (50 mg/liter, Sigma Chemical Company; St. Louis, Missouri, We ex...

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Therapeutic Implications of the Nitric Oxide Pathway in Gastrointestinal Diseases

Tepperman¹,

Whittle²

2000

Drug Development

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Nitric oxide counteracts 5-hydroxytryptamine- and cholera toxin-induced fluid secretion and enhances the effect of oral rehydration solution

Cited by 21 publications

References 17 publications

Nitric Oxide Produced by the Enterocyte Is Involved in the Cellular Regulation of Ion Transport

Nitric Oxide Produced by the Enterocyte Is Involved in the Cellular Regulation of Ion Transport

Compartmentalization of extracellular cGMP determines absorptive or secretory responses in the rat jejunum

Therapeutic Implications of the Nitric Oxide Pathway in Gastrointestinal Diseases

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