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PubMed1982

The effect of stimulating somatic afferents on cholera secretion in the rat small intestine.

The effect on rate of cholera secretion in the small bowel of activation of the group III and A delta afferent fibres in the sciatic nerve was studied in rats. Activation of these fibres at 3 Hz for 60 min significantly diminished choleraic secretion from 121 +/- 29 to 25 +/- 9 microliters x min-1 x 100 cm-2 serosal surface (mean +/- SE; n = 9). The effect was apparent after the nerve stimulation. Stimulation of the sciatic nerve had no significant effect on choleraic fluid secretion after interrupting the autonomic nerves to the intestine, nor did it significantly alter net fluid transport in non-choleraic intestine with intact nervous supply. It is proposed that the observations may explain the clinical reports of an effect of acupuncture on cholera secretion.

Afferent Pathways↗
PubMed1990

The role of angiotensin-converting enzyme in the rat epididymis.

In order to investigate the role of renin angiotensin in the epididymis, angiotensin-converting enzyme (ACE) activity and angiotensin I (AI) and angiotensin II (AII) concentrations were measured in the male reproductive tract and blood serum of the rat. High ACE activity was detected in the rat epididymis, with a major part of the activity being associated with epididymal spermatozoa. When spermatozoa were prevented from entering the epididymis by efferent duct ligation, the ACE activity in the epididymis was greatly reduced. The epithelial cells lining the epididymal duct were also shown to possess ACE activity which was dependent upon circulating androgens. Treatment of male rats with captopril at a single oral dose (20 mg/kg) significantly inhibited the ACE activity in the blood serum but had no effect on the activity of the epididymal fluid. The intraluminal ACE was protected from the circulating captopril by the blood-epididymis barrier. Long-term treatment with captopril (20 mg/kg per day, 8 weeks), however, caused an increase in blood serum ACE activity but was without effect on intraluminal ACE. The fertility and fecundity of male rats after treatment were apparently normal. The concentrations of AI and AII were high in the epididymal plasma and epididymal cell when compared with the respective concentrations in blood serum. The intraluminal AII concentration found (13 nmol/l) was close to the threshold concentrations that stimulate anion (and fluid) secretion in cultured epididymal epithelium in vitro. The high intraluminal AII concentration could not have been derived from the testicular fluid or spermatozoa since the rete testis fluid and sperm contained little AII.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin I↗
PubMed2000

Production of heat-labile enterotoxin by strains of Aeromonas veronii bv veronii.

Three isolates of Aeromonas veronii bv veronii (2 environmental, one blood infection) were examined to see if they produce any enterotoxin and, if so, to determine its characteristics. Two isolates caused fluid accumulation in the initial rabbit ileal loop tests. The other strain did so after a single passage through the rabbit ileal loop. All the isolates showed gradual enhancement of fluid secretion after each subsequent passage. Inocula of 1 x 10(4) viable cells and 0.25 mL of culture filtrate caused fluid accumulation comparable to those of toxigenic Vibrio cholerae 569B. The enterotoxic activity was inactivated at higher temperature, and showed biological activity over a wide range of pH. The only histopathological change observed was depletion of mucous from goblet cells. The findings of the study indicate that strains of A. veronii bv veronii produce a heat-labile, pH-stable diarrhoeagenic factor without causing any damage to the intestinal mucosa.

Aeromonas↗
PubMed2006

Regulatory interaction between CFTR and the SLC26 transporters.

Most epithelia that express CFTR secrete fluid rich in HCO3- and poor in Cl- that is generated by a CFTR-dependent Cl- absorption and HCO3- secretion process that when aberrant leads to human diseases such as cystic fibrosis and congenital chloride diarrhoea. Epithelial Cl- absorption and HCO3- secretion require expression of CFTR and other Cl- and HCO3- transporters in the luminal membrane of the secreting cells. Recent advances in understanding this critical epithelial function revealed that the luminal Cl- and HCO3- transporters are members of the SLC26 family. Characterization of several members of the family reveals that all characterized thus far are electrogenic with an isoform specific Cl-/HCO3- transport stoichiometry. In vivo these transporters exist in a transporting complex with CFTR. The SLC26 transporters and CFTR are recruited to the complex by binding to scaffolds containing PDZ domains. Upon stimulation and PKA-dependent phosphorylation of CFTR R domain, the R domain binds to the SLC26 transporter STAS domain. Interaction of the R and STAS domains results in a marked and mutual activation of CFTR and the SLC26 transporters. The significance of this mode of regulation to epithelial Cl- absorption and HCO3- secretion is obvious.

Animals↗
PubMed1982

Control of renal function in freshwater and marine teleosts.

The glomerular filtration rate (GFR) of teleost fishes is highly variable and is influenced by glomerular intermittency, environmental salinity, renal perfusion pressure, and some hormones. In freshwater (FW) teleosts, the primary function of the kidney is to excrete excess water while retaining most of the filtered solutes, and GFR is a major determinant of urine flow. Low permeability to water prevails in the distal nephron of FW teleosts, and the majority of the filtered Na and Cl is reabsorbed without osmotic accompaniment of water. Prolactin appears to regulate osmotic permeability to water. Isolated and perfused distal tubules from FW teleosts revealed a transepithelial voltage (Vt) that was positive in the lumen. Both Na and Cl participate in generating lumen-positive Vt. Marine teleosts, which are exposed to Na loading and dehydration, ingest seawater to compensate for their osmotic water loss, and secrete divalent ions, mainly Mg and SO4, from the kidney. The urine flow of marine teleosts is primarily determined by fluid secretion accompanied by divalent ions and subsequent isosmotic reabsorption with NaCl. Interdependence of Na and Cl transport has been noted in the urinary bladder of marine teleosts. There is presently no known humoral substance that regulates NaCl and divalent ion transport in the teleost kidney.

Animals↗
PubMedDate not supplied

Effects of tropisetron, a 5-hydroxytryptamine type 3 receptor blocker, on intestinal secretion induced by cholera toxin or deoxycholic acid in rabbits in vivo.

It has been suggested that 5-hydroxytryptamine is involved in the pathogenesis of various intestinal hypersecretory states including cholera. In this study, the effect of tropisetron (ICS 205-930), a specific 5-hydroxytryptamine type-3 receptor blocker, on jejunal and colonic fluid secretion induced respectively by cholera toxin and deoxycholic acid was investigated in rabbits using isolated loops of intestine in vivo. Marked fluid accumulation in both the jejunal and colonic loops was observed after exposure to cholera toxin and deoxycholic acid respectively. Elevation of jejunal and colonic mucosal cyclic adenosine monophosphate concentrations was also noted. Intraperitoneal administration of tropisetron dose-dependent inhibited jejunal secretion induced by cholera toxin. In contrast, no significant anti-secretory effect of tropisetron was observed against colonic secretion induced by deoxycholic acid. Tropisetron did not affect elevated mucosal cyclic adenosine monophosphate concentrations. The inhibitory effect of tropisetron on intestinal secretion induced by cholera toxin, which was independent of cyclic adenosine monophosphate formation, suggests that 5-hydroxytryptamine plays an important role in this type of secretion.

Animals↗
PubMed1989

Selective precipitation of 14 kDa stone/thread proteins by concentration of pancreaticobiliary secretions: relevance to pancreatic ductal obstruction, pancreatic failure, and CF.

Concentrated proteins in pancreatic juice could precipitate and plug pancreatic ducts, initiating pancreatic disease. In cystic fibrosis (CF), pancreatic fluid secretion is impaired due to defective anion transport and proteins are hyperconcentrated. To determine whether proteins in pancreatic secretions precipitate selectively or nonspecifically, duodenal secretions were obtained from subjects with and without cystic fibrosis, during pancreatic stimulation with cholecystokinin (CCK) and secretin, dialyzed against phosphate-buffered saline (PBS), and concentrated in stages by ultrafiltration. Precipitates obtained by centrifugation at 15,600 g for 10 min at 4 degrees C were analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The only protein band regularly enriched in precipitates from 10 CF and 9 non-CF samples had an Mr of approximately 14,000. Monoclonal antibodies, raised independently in two laboratories against either pancreatic stone protein (PSP) or pancreatic thread protein (PTP), reacted with the Mr 14,000 protein(s). Differential extraction of PTP and PSP by 0.1N HCl and 10% sodium citrate produced Mr 14,000 products that reacted equally with each monoclonal antibody (MAB). Two-dimensional gel electrophoresis demonstrated two Mr 14,000 spots in each extract with pI's of 5.8 and 6.0. Each spot reacted equivalently with the MABs for PSP and PTP. PSP/PTP type proteins are sparingly soluble in pancreatic secretions and could contribute to protein plugging in pancreatic disease.

Blotting, Western↗
PubMed1985

Choice of anesthetic for intestinal absorption and secretion experiments using rats.

The net rates of glucose and water absorption from, and secretion of water into, the lumen of the rat small intestine were compared using alpha-chloralose, halothane, pentobarbitone, and urethane as anesthetics. Water and glucose transport were determined by recirculation of perfusion fluid through the lumen of the jejunum. Net fluid secretion was stimulated by intraarterial (i.a.) infusion of prostaglandin E1 (PGE1) and vasoactive intestinal peptide (VIP). The results show that the anesthetics used exert only minimal influence on the physiological rates of glucose and water absorption and there is no correlation between the small differences in glucose and water absorption among the anesthetics. However, when the fluid secretory mechanism of the mucosa is stimulated with either PGE1 or VIP, pentobarbitone allows the greatest rates of secretion, but halothane prevents secretion. It is suggested that of the anesthetics used, pentobarbitone is the most appropriate for intestinal secretion experiments.

Alprostadil↗
PubMed1976

Enzyme-cytochemistry of the saccus dorsalis of the rainbow trout, Salmo gairdneri Richardson.

In the saccus dorsalis of the rainbow trout, Salmo gairdneri Richardson, the activity of various enzymes (transferase, lyases, oxidoreductases, hydrolases) have been studied in detail. The results of this enzyme-cytochemical study firmly demonstrate that the organ is metabolically highly active. The epithelial cells have a strong energy metabolism. Energy production can take place under aerobic as well as under anaerobic conditions. Evidence is presented that glucose from blood is directly utilized for energy demands. The epithelial cells show also high synthetic activities. The moderate amino acid metabolism may participate in the synthesis of an acid mucopolysaccharide-protein complex, especially in the so-called dark cells. Lipid metabolism appears to be restricted to the mitochondria, indicating a high turnover of lipid moieties in the membranes. In contrast to the normal looking mitochondria, the macromitochondria--besides shape and localization--have an extremely high lipid and monoamine metabolism, which may point to a special function in the cellular economy. The high activity of enzymes involved in the degradation of monoamines and in the hydration of CO2 is of particular physiological interest. The significance of the observations is discussed in relation to formerly obtained indications on the involvement of the saccus dorsalis in fluid secretion, extrusion of organic substances of low molecular weight into the ventricular system and uptake of organic substances from the cerebrospinal fluid. The hypothesis of the saccus dorsalis being an analogue of the choroid plexus is supported by several relevant data.

Animals↗
PubMed1990

Influence on intestinal secretion of eicosanoids.

Eicosanoids have been shown to be important modulators of intestinal secretion. In cholera, cAMP is often regarded as the sole mediator, but recent data suggest that 5-hydroxytryptamine (5-HT) and prostaglandin (PG) E2 also play important roles. Thus cholera toxin (CT) increases their release from the rat jejunum in vivo, and human cholera is associated with an increased luminal 'overflow' of PGE2. In vitro evidence of secretion can be obtained with PG concentrations 100- to 1000-fold lower than those required for activation of the adenylate cyclase. Furthermore, 5-HT induces secretion associated with increased 'overflow' of PGE2, but without a change in mucosal cAMP. CT-induced release of PGE2 and fluid secretion can be decreased by indomethacin or by the 5-HT2-receptor antagonist, ketanserin, whereas the release of 5-HT and cAMP is not affected by either substance. Secretion caused by vasoactive intestinal polypeptide (VIP) is associated with increased mucosal cAMP levels, without a change in PGE2 release, and is unaffected by indomethacin and ketanserin. These results suggest that CT stimulates the release of 5-HT, which in turn causes the release of PGE2. The latter substances probably act via a local intramural reflex and contribute to secretion by mechanisms that are independent of cAMP.

Animals↗
PubMed1986

Effect of toxin A and B of Clostridium difficile on rabbit ileum and colon.

The effect of purified toxin A and partially purified toxin B on rabbit ileum and colon was investigated. Toxin A caused tissue damage which was followed by permeability changes and fluid accumulation in both tissues. Toxin A did not increase the permeability of the colon to the extent observed for ileum; secreted fluid contained less protein of plasma origin. Toxin B had no effect on either tissue. Secretory and tissue damaging properties of crude C difficile toxins were found to be due to toxin A.

Animals↗
PubMed1985

Cl- requirement for saliva secretion in the isolated, perfused rat submandibular gland.

Replacement of perfusate Cl- with Br- reduced by 37% the volume of saliva secreted by isolated, perfused rat submandibular glands exposed to 10(-6) M acetylcholine. Replacement of perfusate Cl- with SO4(2-) reduced fluid secretion by 73%, while replacement of bicarbonate with HEPES or addition of acetazolamide had no effect on salivary flows or volumes. Furosemide (10(-3) M) reduced saliva secretion when added to Cl- -(73%) or Br- -containing (56%) perfusates and also to HEPES- (95%) or acetazolamide-containing (82%) perfusates. Perfusion of the glands with furosemide or SO4- containing perfusates resulted in significantly reduced salivary Cl- concentrations and increased residual anion (Na+-K+-Ca2+-Cl-) concentrations, while perfusion with solutions containing acetazolamide or with HCO3- -free (HEPES) perfusates resulted in opposite changes in salivary anions. Addition of furosemide to HEPES- or acetazolamide-containing perfusates reversed these changes and caused a reduction in salivary Cl- concentrations and an increase in residual anion concentrations. It is concluded that 1) extracellular Cl- is required for saliva secretion in the rat submandibular gland, 2) the required external Cl- enters the salivary cells by a furosemide-sensitive transport system, which is likely to be similar to a Na+-K+-Cl- cotransport system described in other epithelia, 3) HCO3- is not normally required for saliva secretion but can sustain it partially when Cl- transport is inhibited by either furosemide or Cl- replacement, and 4) salivary electrolyte changes induced by Cl- or HCO3- replacement or by furosemide probably represent combined effects on acinar secretion and transductal electrolyte transport.

Animals↗
PubMed2000

Gastric acid secretion in aquaporin-4 knockout mice.

The aquaporin-4 (AQP4) water channel has been proposed to play a role in gastric acid secretion. Immunocytochemistry using anti-AQP4 antibodies showed strong AQP4 protein expression at the basolateral membrane of gastric parietal cells in wild-type (+/+) mice. AQP4 involvement in gastric acid secretion was studied using transgenic null (-/-) mice deficient in AQP4 protein. -/- Mice had grossly normal growth and appearance and showed no differences in gastric morphology by light microscopy. Gastric acid secretion was measured in anesthetized mice in which the stomach was luminally perfused (0. 3 ml/min) with 0.9% NaCl containing [(14)C]polyethylene glycol ([(14)C]PEG) as a volume marker. Collected effluent was assayed for titratable acid content and [(14)C]PEG radioactivity. After 45-min baseline perfusion, acid secretion was stimulated by pentagastrin (200 microg. kg(-1). h(-1) iv) for 1 h or histamine (0.23 mg/kg iv) + intraluminal carbachol (20 mg/l). Baseline gastric acid secretion (means +/- SE, n = 25) was 0.06 +/- 0.03 and 0.03 +/- 0.02 microeq/15 min in +/+ and -/- mice, respectively. Pentagastrin-stimulated acid secretion was 0.59 +/- 0.14 and 0.70 +/- 0.15 microeq/15 min in +/+ and -/- mice, respectively. Histamine plus carbachol-stimulated acid secretion was 7.0 +/- 1.9 and 8.0 +/- 1.8 microeq/15 min in +/+ and -/- mice, respectively. In addition, AQP4 deletion did not affect gastric fluid secretion, gastric pH, or fasting serum gastrin concentrations. These results provide direct evidence against a role of AQP4 in gastric acid secretion.

Animals↗
PubMed2003

Nasal epithelium potential difference at high altitude (4,559 m): evidence for secretion.

Hypoxia inhibits activity and expression of ion transport proteins of cultured lung alveolar epithelial cells. Here we tested, whether in vivo hypoxia at high altitude (4,559 m) also inhibits lung ion transport. Transepithelial nasal potentials (NP) were determined as a surrogate measure of lung ion transport activity before and during the stay at altitude. In normoxia, total NP was approximately 20% higher in control subjects than in susceptibles to high-altitude pulmonary edema, but there was no difference between groups in amiloride-inhibitable NPs. At high altitude total NP increased 250% in both groups, whereas amiloride-sensitive NP decreased in control subjects only (-80%), and the chloride ion (Cl-)-sensitive portion of NP almost doubled. Because many mountaineers suffer from nasal dryness at high altitude, a control study was performed in normobaric hypoxia (12% oxygen, 6 hours) at a controlled humidity of 50%. In this study, no change in total NP or its amiloride- and Cl-sensitive portions was observed. The increased Cl- secretion at high altitude but no such change in normobaric hypoxia suggests that nasal dryness may stimulate local active Cl- and fluid secretion in the upper respiratory tract. It is therefore uncertain whether similar changes also occur at the alveolar epithelium.

Adult↗
PubMed1971

Ion transport during cholera-induced ileal secretion in the dog.

To assess the ion transport mechanism by which cholera causes the small bowel to secrete, ion transport rates and electrical potential difference (PD) were determined simultaneously in the normal and choleragen-treated dog ileum in vivo. The results indicate that, during cholera, HCO(3) is actively secreted (i.e., against both an electrical and a concentration gradient); Cl is also actively secreted, against a modest electrochemical gradient. Electrogenic pumping of one or both of these anions is probably responsible for an observed PD change of approximately 13 mv (lumen negative). Na secretion can be accounted for entirely by passive ion movement. K secretion can be partly explained by passive diffusion secondary to the negative intraluminal PD; however, its concentration in the secreted fluid is two to three times higher than expected on the basis of passive forces, suggesting a component of active K secretion. The PD response of the choleragen-treated ileum is normal in response to glucose, but there was no PD response to saline-free mannitol perfusion. This suggests that the normal differential permeability of the ileum to anions and cations may be altered by choleragen, although other explanations of this finding are also possible.

Animals↗
PubMed1989

Development of intestinal host defense: an increased sensitivity in the adenylate cyclase response to cholera toxin in suckling rats.

To determine if developmental variations existed in the second messenger system that mediates cholera toxin (CT) action, the adenylate cyclase (AC) response was studied in 2-wk-old suckling and 6-wk-old weaned rats. AC was assayed in the proximal small intestine 4 h after intraduodenal administration of various doses of CT. Dose-effect analysis showed a 9-fold increase in the sensitivity of the CT-activated cyclase response in suckling rats when measured by the ED50, expressed as microgram CT/g body wt (0.03 for 2 wk, 0.27 for 6 wk). When the CT dose was expressed as microgram/animal, suckling rats were 50 times more sensitive than 6-wk-old rats. In addition, the CT-induced fluid secretion was closely correlated with the elevated cyclase activities (correlation coefficient: 0.83 for 2 wk, 0.93 for 6 wk). Furthermore, more fluid seemed to be secreted/unit wt of gut in the sucklings, even when the same level of enzyme activity was compared. A maximum of 3- to 4-fold rise in AC activation occurred at 0.5 microgram CT/g body wt, but both the basal and the maximal stimulated levels of AC were not developmentally different. This study demonstrates an in vivo increase in AC responsiveness to CT that may be in part responsible for the increased incidence of toxigenic diarrhea in neonates.

Adenylyl Cyclases↗
PubMed2006

Downregulation of aquaporins 1 and 5 in nasal gland by osmotic stress in ducklings, Anas platyrhynchos: implications for the production of hypertonic fluid.

Using primers against highly conserved regions of mammalian and bird aquaporins in RT-PCR experiments, we amplified products derived from duck (Anas platyrhynchos) nasal gland RNA that were identified as homologues of mammalian and chicken aquaporin 1 and aquaporin 5 cDNAs by sequencing. Using digoxigenin-labelled probes derived from these PCR products in northern blot analyses of mRNA isolated from nasal glands of untreated (naïve) or osmotically stressed ducklings (replacement of drinking water with a 1% NaCl solution), we observed a decrease in aquaporin 1 (AQP1) and aquaporin 5 (AQP5) mRNA abundance (by approximately 40%) during saline adaptation in the animals. Western blot analysis of AQP1 and AQP5 expression in the glands revealed that protein abundance decreased in a similar fashion. Immunohistochemical analysis of AQP1 distribution in cryosections of nasal gland indicated that AQP1 is mainly expressed in endothelial cells of the capillaries, but definitely not in the secretory or ductal cells of the gland. AQP5 distribution in the gland, however, seems to be different, since staining was exclusively observed in apical and basolateral plasma membranes of individual epithelial cells of the primary and central ducts, which collect fluid from the secretory tubules. The observations are consistent with the hypothesis that strongly hyperosmotic fluid is produced by the secretory cells at very low (unstimulated gland) or high (activated gland) rates. In the unstimulated gland, secretions may be diluted by aquaporin-mediated transcellular water flux while passing through the ductal system flushing the glandular ducts, thereby potentially preventing ascending infections. In the activated gland, however, downregulation of aquaporins in capillaries and duct cells may prevent dilution of the initially secreted fluid, enabling the animals to excrete large volumes of a highly concentrated salt solution.

Amino Acid Sequence↗
PubMed1978

The effect of adsorbant and anti-inflammatory drugs on secretion in ligated segments of pig intestine infected with Escherichia coli.

Four adsorbant drug preparations, Kaopectate, colloidal Attapulgite, noncolloidal Attapulgite and Pepto-bismol were investigated for their effects on fluid accumulation in ligated segments of pig intestine inoculated with enteropathogenic Escherichia coli. Two anti-inflammatory drugs. aspirin and methylprednisolone, and two antibiotics, lincomycin and polymyxin B, were also tested. All the drugs except the two anti-inflammatory products were given by injection into the lumen of the intestine. Aspirin was given orally and methylprednisolone was given intramuscularly. The antibiotics were tested at levels at which they had no significant antibacterial effect in in vitro tests. The adsorbant drugs colloidal Attapulgite and Pepto-bismol were shown to be effective in reducing fluid accumulation in ligated segments of pig intestine infected with enteropathogenic E. coli. In the case of Peptobismol this effect was associated with an antibacterial effect as well as an antitoxic effect, probably due to its adsorbant properties. It is possible that an aspirin-like effect in the gut due to the active ingredient bismuth subsalicylate may have contributed to the effectiveness of Pepto-bismol. Colloidal Attapulgite was demonstrated to have an antitoxic effect but did not have an antibacterial effect. In high doses, the anti-inflammatory drugs acetylsalicylic acid and methylprednisolone were marginally effective in reduction of fluid accumulation in the same test system. Lincomycin was shown to reduce intestinal fluid secretion, whereas polymyxin B had no effect.

Animals↗