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PubMed1999

Surface pH at the basolateral membrane of the caecal mucosa of guinea pig.

Since the major mechanisms responsible for regulation of intracellular pH of enterocytes are located in the basolateral membrane, respective effects may be expected on pH in the compartment near the basolateral membrane. A method was established to estimate the pH at the basolateral membrane (pHb) of isolated caecal epithelia of guinea pig using pH-sensitive fluorescein attached to lectin (lens culinaris). In the presence of bicarbonate and a perfusion solution-pH of 7.4, pHb was 7.70 +/- 0.15. In the absence of bicarbonate or chloride as well as by inhibition of the basolateral Cl--HCO-3 exchange with H2-DIDS, pHb was reduced near to solution-pH. Inhibition of the basolateral Na+-H+ exchanger by adding a sodium- and bicarbonate-free, low-buffered solution increased pHb. Decrease of pH of serosal perfusion solution to 6.4 provoked a similar decrease of pHb to solution pH. Short-chain fatty acids (SCFA) added to the mucosal solution caused a slight decrease of pHb. SCFA added to the serosal side alkalized pHb. However, in the presence of bicarbonate pHb returned quickly to the initial pHb, and after removal of SCFA a transient acidification of pHb was seen. These responses could not be inhibited by MIA or H2-DIDS. We conclude that no constant pH-microclimate exists at the basolateral side. The regulation of the intracellular pH of enterocytes reflects pHb. The slightly alkaline pHb is due to the bicarbonate efflux. Data support the presence of an SCFA--HCO-3 exchange.

Animals↗
PubMed2000

Primary gastric B cell lymphoma: audit of 82 cases treated with surgery and classified according to the concept of mucosa-associated lymphoid tissue lymphoma.

There has been a trend toward stomach conservation during treatment for primary gastric lymphoma, but surgery ensures accurate pathologic diagnosis through the examination of resected specimens. A histopathologic classification for primary gastric lymphoma had been established with the knowledge that the low grade and high grade components occasionally coexist in a single lesion. Efficacy of this classification as an indicator of biologic behavior and prognosis was evaluated. The classification was performed by reexamining surgically resected specimens from 82 patients with stage IE and IIE gastric lymphoma. Clinical characteristics of the low grade and high grade lymphomas were then evaluated and the survival data analyzed. Despite the larger tumor diameter, the depth of invasion for the low grade type was mostly submucosal, and none had serosal invasion. In contrast, 50% of the high grade type had serosal involvement and were also found to have a higher incidence of node metastasis. Prognosis of the low grade type, a 10-year survival rate exceeding 90%, was significantly better than that of the high grade type. Multivariate analysis revealed that curability of the operation followed by the histopathologic grade were significant independent prognostic factors. Some characteristics of the low grade lymphoma were not consistent with what has been reported in the studies involving stomach-conserving strategies. Investigators are advised to note that the histopathologic grade determined with biopsy specimens alone could be misleading.

Adult↗
PubMed2005

Secretory transport of irinotecan metabolite SN-38 across isolated intestinal tissue.

PURPOSE: The purpose of this study was to investigate the transport mechanisms of transporters that contribute to the intestinal efflux of 7-ethyl-10-hydroxycamptothecin (SN-38). METHODS: The intestinal transport of SN-38 was studied in rat intestinal tissue mounted in Ussing chambers. RESULTS: In the ileum, the level of transport from the serosal layer to the mucosal layer was significantly greater than that from the mucosal layer to the serosal layer, whereas a significant difference was not observed in the jejunum. This secretory transport required metabolic energy and was diminished by sulfobromophthalein. However, mitoxantrone, an inhibitor of breast cancer resistance protein (BCRP), did not affect the ileal secretion of SN-38. CONCLUSIONS: The results suggest that a specific transport system, which is distinct from BCRP, plays a major role in the secretion of SN-38 and that this secretory transport system predominantly exists in the ileum.

Animals↗
PubMed2003

Demographic, autoimmune, and clinical profiles of patients with systemic lupus erythematosus in Oman.

Seventy female and three male Omani systemic lupus erythematosus (SLE) patients are described. At disease onset, 45 (62%) were under 20 years of age, and the remainder were between 20 and 44. Of all cases, 48% were familial. Over 5 years, the cumulative frequencies of autoantibodies was: antinuclear antibodies (ANA) 97%, anti-double-stranded DNA (anti-dsDNA) antibodies 92%, extractable nuclear antigen (ENA) antibodies 64%, antineutrophil cytoplasmic antibodies (ANCA) 58%, antiphospholipid (APL) antibodies 80%, and rheumatoid factor (Rf) 22%. Ribonucleoprotein (RNP) antibodies were found in 15/45 younger-onset and 2/28 older-onset patients (chi(2)=6.63, P<0.02). The mean SLE disease activity score (SLEDAI) was 13.5+11.4, and the cumulative frequencies of systemic involvement were: neurological 33.8%, vascular 10.4%, musculoskeletal 53.9%, renal 50.7%, dermal 80.5%, serosal 23.9%, immunological 95%, constitutional 31.3%, and haematological 26.0%. Linear regression analysis showed that high-titre ANA were predictors for pyuria (odds ratio [OR] 9.06, P=0.01). Antiextractable nuclear antigen antibodies were predictors for disease of the neurological (OR 26.3, P=0.008) and serosal (OR 27.7, P=0.005) systems, and anti-Sm antibodies for alopecia (OR 5.93, P=0.088) and hypocomplementaemia (OR 14.6, P= 0.016). Antibodies of known diagnostic utility may also give insights into the pathogenesis of SLE.

Adolescent↗
PubMed2002

Divalent cations reduce the electrogenic transport of monovalent cations across rumen epithelium.

The rumen epithelium of sheep and goats showed an increase in short circuit current ( Isc) and transepithelial conductance (gt) upon mucosal removal of divalent cations. A divalent-sensitive Isc and gt were present in Na+, K+ or Rb+ buffer, but nearly abolished in mucosal NMDG+ (N-methyl-D-glucamine) buffer. High K buffer, addition of BaCl2 or of ouabain on the serosal side also reduced or abolished the divalent-sensitive Isc. Mucosal Ca2+ was more potent in blocking Isc, but had the same potency as Mg2+ in blocking gt. A prolonged mucosal deprivation of Mg2+ ions increased gt, potential difference and basal as well as the Ca2+-sensitive Isc. Mucosal addition of Mg2+ had a smaller effect on gt after serosal preincubation with Ba. The data suggest that rumen epithelial cells exhibit an apical non-selective cation conductance, which permits the passage of monovalents in the mucosal absence of divalents. The development of a divalent-sensitive Isc in Na buffer requires Na+/K+ pumps and K+ recycling through Ba2+-sensitive K+ conductances on the basolateral side. This Isc is blocked by extracellular Ca2+ and both extracellular and intracellular Mg2+ ions. A prolonged deprivation of mucosal Mg2+ alone seems to affect intracellular Mg2+ in this Mg2+-absorbing tissue.

Animals↗
PubMed2003

Effect of nitric oxide on electrolyte transport across the porcine proximal colon.

The effect of nitric oxide (NO) on ion transport in the porcine proximal colon was investigated in slide-stripped epithelia mounted in Ussing chambers. The serosal addition of the NO-donors sodium nitroprusside (SNP, 0.5 mM) or S-nitroso-N-acetylpenicillamine (SNAP, 0.5 mM) induced a steep increase of short-circuit current ( I(sc)). The stimulatory effect of SNP on I(sc) could not be blocked by piroxicam or tetrodotoxin. Potassium channel inhibitors (quinidine, tetraethylammonium or barium) added serosally reduced the SNP- or SNAP-induced increases of I(sc). In chloride-free solutions, the SNP-induced increase of I(sc) was smaller than in chloride-containing solutions. Cl(- )and Na(+) flux measurements demonstrated that SNP diminished Cl(-) and Na(+) net absorption. Pre-treatment with barium was able to block the inhibitory effect of SNP on NaCl net absorption totally. NO effects on paracellular pathways were assessed by measuring flux rates of [(14)C]-D-mannitol. SNP did not change unidirectional D-mannitol flux rates. In conclusion, NO inhibits NaCl net absorption in the proximal colon of pigs by acting directly on the enterocyte. The antiabsorptive (and/or prosecretory) effect of NO depends on a functional basolateral potassium conductance.

Animals↗
PubMed2006

Transepithelial transport of zinc and L-histidine across perfused intestine of American lobster, Homarus americanus.

The intestine of the American lobster, Homarus americanus, was isolated and perfused in vitro with a physiological saline, based on the ion composition of the blood, to characterize the mechanisms responsible for transmural transport of zinc and how the amino acid, L-histidine, affects the net movement of the metal across the tissue. Previous studies with this preparation, focusing on the characteristics of unidirectional mucosa to serosa (M to S) fluxes of (65)Zn(2+) and (3)H-L-histidine, indicated the presence of a brush border co-transport process responsible for simultaneously transferring the metal and amino acid across this tissue as an apparent bis-complex (Zn-[His](2)) using a PEPT-1-like dipeptide carrier mechanism. In addition, both zinc and L-histidine were also transferred toward the blood by separate transporters that were independent of the other substrate. The focus of the present study was to characterize the serosa to mucosa (S to M) flux of (65)Zn(2+) under a variety of conditions, and use these values in conjunction with those from the previous study, to assess the direction and magnitude of net metal movement across the tissue. Transmural S to M transport of (65)Zn(2+) was markedly reduced with the addition of the serosal inhibitors ouabain (32%), excess K(+) (25%), excess Ca(2+) (30%), Cu(2+) (38%), nifedipine (21%), and vanadate (53%). In contrast, this flux was markedly stimulated with the serosal addition of ATP (24%) and excess Na(+) (28%). These results suggest that S to M fluxes of zinc occurred by the combination of the basolateral Na/Ca exchanger (NCX), where zinc replaced calcium, and a basolateral nifedipine-sensitive calcium channel. Transmural M to S (65)Zn(2+) fluxes (5-100 microM) were threefold greater than S to M metal transport, and the addition of luminal L-histidine doubled the net M to S zinc flux over its rate in the absence of the amino acid. The results of this paper and those in its predecessor indicate that zinc transport by the lobster intestine is absorptive and significantly enhanced by luminal amino acids.

Adenosine Triphosphate↗
PubMed2001

Influence of isoform and DNP on butyrate transport across the sheep ruminal epithelium.

Short-chain fatty acids are absorbed in considerable amounts from the rumen. During transit through the epithelial layer, they are intensively metabolised. Interaction between intraepithelial metabolism and absorption, however, is hardly understood. The present study therefore compared the transepithelial transport of the easily metabolised n-butyrate with that of the more metabolism-resistant iso-butyrate both under in vivo conditions (isolated and washed reticulorumen) and in vitro conditions (Ussing chamber). Under in vivo conditions, net absorption of n-butyrate was significantly higher than that of iso-butyrate. The in vitro experiments showed that the higher net flux of n-butyrate was solely due to a higher mucosal-to-serosal flux, whereas the serosal-to-mucosal flux of butyrate was independent from the isoform. Blocking intraepithelial ATP delivery by 2,4-dinitrophenol abolished the net flux of n-butyrate. The study indicates that metabolism and/ or ATP availability stimulates n-butyrate net absorption. By this, the metabolic activity of the epithelium may have a regulatory influence on absorption of n-butyrate.

2,4-Dinitrophenol↗
PubMed2004

Local dexamethasone improves the intestinal lesions of gastroschisis in chick embryos.

BACKGROUND AND AIMS: Eviscerated bowel in gastroschisis (Gx) undergoes changes that lead to dysfunctions and create management difficulties. This study tests the hypothesis that exposure of the eviscerated bowel of chick embryos with Gx to dexamethasone might have beneficial effects on the parietal lesions. METHODS: Gx was created in chick embryos on incubation day 15 and either dexamethasone (0.047 mg in 0.24 ml) or 0.075% saline were instilled into the amnio-allantoic chamber on day 17. The chicks were recovered near hatching (day 19) and eviscerated and non-eviscerated portions of the intestines were recovered, weighed and processed for HE and synaptophysin staining or for total DNA and protein measurements. Total mural and serosal layer thickness were determined and intramural ganglia were counted. ANOVA was used for comparison among groups with significance level set at p<0.05. RESULTS: Chicks with Gx and Gx + saline controls had reduced body weight and tibial length in comparison with controls. The eviscerated bowel was heavier with marked wall thickening at the expense of all layers but particularly of the serosa. They had decreased total intestinal DNA with normal protein and decreased intramural ganglion density. In contrast, chicks from the Gx + dexamethasone group had normal body weight and tibial length, near-normal intestinal wall thickness with slightly increased serosal width, near-normal intestinal DNA content and normal density of intramural ganglia. CONCLUSION: Local dexamethasone had beneficial effects on the eviscerated bowel of chicks with Gx as judged by decreased wall thickening, normalization of total intestinal DNA and richer neural population. Late gestational exposure to steroids could represent another alternative for preventing intestinal lesions in Gx.

Administration, Topical↗
PubMed2003

Protective fibrin-sealed plication of the small bowel in recurrent laparotomy.

PURPOSE: Adhesions after recurrent abdominal operations remain extremely common and are sources of severe morbidity. Fibrin-glued plication of the small gut in a meander-like formation is supposed to guarantee a decreased risk of intestinal obstruction postoperatively. This retrospective study analyses the clinical outcome after recurrent laparotomy in children treated with bowel plication by fibrin sealant. METHODS: The surgical technique of performing the fibrin-glued plication is rather simple and quick: after taking off all adhesions two to four loops of the small gut are positioned so that they lie side by side. Beginning proximal fibrin [Tissucol fibrin sealant (Baxter)] is applied between the loops; approximately 20-30 s are needed to keep the loops in position until the fibrin dries. This manoeuvre is continued until all of the small gut is fixed in one block. The gut is brought back into the abdominal cavity without loosening the loops. This fixed formation by sero-serosal adhesions or mesenterial plications is supposed to guarantee postoperative free passage. The charts of 60 children who had undergone a fibrin plication of the small bowel between 1991 and 1999 were evaluated. Additionally, questionnaires were sent to all patients, and they were invited for an examination. RESULTS: Sixty patients (38 boys and 22 girls) received a fibrin sealant plication because of recurrent laparotomies with heavily serosal defects or recurrent ileus because of adhesions. The youngest baby was 10 days. Since 23 patients were premature the oldest patient was 11 years old. There were no intraoperative complications attributed to the method. In the postoperative period 7/60 (12%) patients had a recurrent ileus or subileus, leading in three (5%) patients to an early relaparotomy. CONCLUSION: The fibrin-glued plication of the small bowel decreases the risk of recurrent ileus or subileus considering the high figures in the literature concerning this issue. The time-saving method is very simple and easily feasible. No side effects after the treatment with fibrin glue were observed.

Child↗
PubMed2003

The effect of hyperbaric oxygen treatment on the inflammatory changes caused by intraperitoneal meconium.

Exposure of the peritoneal cavity to meconium causes a marked inflammatory response. The effect of intraperitoneal meconium on intestinal morphology and plasma nitrite and nitrate (NO2(-) + NO3(-)) levels and how this inflammatory process is influenced by hyperbaric oxygen (HBO) treatment were investigated in this study. The purpose was to determine whether HBO treatment could be considered a useful adjunct in the resuscitative treatment of severely ill patients admitted with meconium peritonitis (MP). Rats were divided into three groups. Human meconium (MP group, n=10) and sterile saline (control group, n=10) were injected intraperitoneally for 3 days. The procedure for meconium injection was combined with HBO treatment for the HBO group (n=10). HBO was administered for 7 days. In all groups, peritoneal swap cultures, plasma NO2(-) + NO3(-) levels, intestinal diameters, and macroscopic and microscopic changes in the intestine were determined on the 8th day. Bacterial growth was not detected in the peritoneal swap cultures. There was a significant difference in NO2(-) + NO3(-) levels between the MP and HBO groups ( P<0.05), between the MP and control groups ( P<0.01), and between the HBO and control groups ( P<0.05). Thin fibrinous adhesions in both the MP and HBO groups, and thickened and dilated intestinal loops in the MP group were observed macroscopically. The intestinal diameter in the MP group was significantly greater than in the HBO and control groups. The only microscopic difference was seen in the serosal layer. Compared with the animals in the control and HBO groups, the intestine of the rats in the MP group showed prominent serosal thickening, edema, capillary proliferation and cellular infiltration. The ameliorated inflammatory changes and decreased dilatation of the intestine accompanied by a significant decrease in NO2(-) + NO3(-) levels suggest that as an adjunctive treatment, HBO may have a beneficial effect in the resuscitative treatment of meconium peritonitis.

Animals↗
PubMed2000

The acute scrotum in Arab children with familial Mediterranean fever.

Over a period of 7 years, among 175 boys under the age of 16 years with familial Mediterranean fever (FMF), 16 (9%) developed 28 episodes of scrotal swelling that was unilateral in 26 (93%) and bilateral in 2 (7%). Fever and pain were present in 15 (94%) children; fever was characterized by a gradual onset and pain was moderate in intensity. The episodes were self-limiting and lasted from 8 h to 5 days. Scrotal swelling was the presenting feature of FMF in 4 (25%) patients. Six (38%) children underwent surgery; the operative findings, available in 3, showed a normal testis and epididymis and inflammation of the tunica vaginalis. The self-limiting nature of the episodes lasting for a few days was similar to the clinical course of serositis seen in FMF. This strongly suggests that inflammation of the tunica vaginalis, resulting in scrotal swelling, is another feature of FMF serositis. The gradual onset of fever, pain, swelling, and recurrence in a boy of Mediterranean origin, especially in the presence of a relevant family history, strongly points toward the diagnosis of FMF and conservative management. Early diagnosis and prophylactic colchicine therapy are expected to avert recurrences, which may result in ischemic testicular necrosis and FMF nephropathy.

Abdominal Pain↗
PubMed2003

Liquid antiadhesive product (Adcon-p) prevents post-operative adhesions within the intra-abdominal organs in a rat model.

BACKGROUND AND AIMS: Postoperative adhesions mostly cleave to small bowel and lead to troublesome problems. This study evaluated the effectiveness of a novel liquid antiadhesive product (Adcon-P) in rats. SUBJECTS AND METHODS: Thirty-eight Sprague Dawley rats underwent laparotomy during which the surgeon created abrasions on five different small bowel locations and the cecum in order to generate adhesions. Rats were randomly assigned to receive Adcon-P ( n=19) or to a control group ( n=19). The animals were killed on postoperative day 21. An observer blinded to the randomization assessed the difficulty of adhesiolysis with a six-point scoring system, recorded locations of adhesions and, noted the presence of serosal and full-thickness injuries. The total number of adhesions was also chronicled. RESULTS: The severity of adhesion and adhesion scores were significantly lower in animals receiving Adcon-P. More animals suffered full-thickness and serosal injuries in the control group. The adhesions between small bowel segments and the number of adhesions attached to the small bowel were significantly lower in animals that received Adcon-P. CONCLUSION: Adcon-P leads to an easier adhesiolysis and lessens the risk of bowel injury during relaparotomy. In particular, Adcon-P reduces the probability that adhesions specifically attach to the small bowel.

Animals↗
PubMed2000

Bidirectional supply of glutamine maintains enterocyte ATP content in the in vitro using chamber model.

Glutamine is the principal energy source for enterocytes, but it is not known whether parenteral or enteral supplementation is most beneficial to gut integrity. The aim of this study was to evaluate the effects of glutamine in uni- or bidirectional supply on the viability of intestinal mucosa of starved rats during incubation in Ussing chambers. Segments of jejunum from rats starved for 48 h were randomly mounted in Ussing chambers with three nutrient solutions: Krebs buffer without glutamine; 6 mM glutamine added to the mucosal side; 6 mM glutamine added to the mucosal side and 0.6 mM glutamine to the serosal side. ATP content of the mucosa, electrophysiology, and 51Cr-ethylenediaminetetraacetate (EDTA) permeability were studied during 180 min of incubation. The addition of glutamine to both sides of the stripped mucosa improved ATP levels compared to the Krebs solution (P < 0.05), and the addition of glutamine resulted in an increase in short circuit current (P < 0.05). No significant differences were seen in 51Cr-EDTA permeability or epithelial electrical resistance. Glutamine supplementation to both the luminal and serosal side in the Ussing chamber was more effective than luminal glutamine only in maintaining ATP levels of intestinal mucosa. Bidirectional supplementation of glutamine might improve intestinal energy metabolism and viability in in vitro studies.

Adenosine Triphosphate↗
PubMed1997

Localization of membrane-associated sialomucin on the free surface of mesothelial cells of the pleura, pericardium, and peritoneum.

Strong anionic sites, as recognized by deposition of cationic colloidal iron even at pH 1.5, were distributed on the free surfaces of the mesothelia of the mouse pleura, pericardium, and peritoneum. Methylation inhibited colloidal iron staining on the surface, and successive saponification restored it. Digestion with neuraminidase or hydrolysis of sialic acid with H2SO4 erased the colloidal iron staining. Lectin Limax flavus agglutinin (LFA), which is specific for sialic acid, labeled the free surface of the mesothelium. All these findings strongly suggested that the surface substance contained sialic acid. Moreover, prior treatment with LFA inhibited the mesothelial surface stain with colloidal iron. In transmission electron microscopy, the colloidal iron (pH 7.3)-stained substance took the shape of fine strands of 50-300 nm in length. These characteristics of the substance on the mesothelial surface correspond well with biochemical properties of membrane-associated sialomucin, whose strong and abundant negative charges produce repulsive forces between facing serosal surfaces. This may contribute to prevent serosal adhesion and to reduce friction during movements of organs.

Animals↗
PubMed1998

alpha1-adrenoceptors antagonize activated chloride conductance of amphibian skin epithelium.

The effects of adrenoceptor agonists on the transepithelial Cl- conductance (GCl) in the skin of several amphibian species, both toads and frogs, were studied. Epinephrine (Epi) from the serosal side selectively and reversibly inhibited the voltage-activated GCl in toad skin and the short-circuit GCl in frog skin. The main effects of activation of the adrenoceptors must reside in the skin epithelium and not in the glands, since measurements were made both from intact skins and split epithelia with essentially the same results. Effective concentrations of Epi were variable among individual tissues. GCl was reduced to 34+/-17% (n=46) with 1 micromol/l Epi, but in some tissues 0.1 micromol/l inhibited more than 80% of GCl, whereas some preparations were little influenced at >3 micromol/l Epi. The affected receptor type was identified by the use of the alpha1-agonist phenylephrine, which mimicked the response of Epi at concentrations above 30 micromol/l, whereas the alpha2-agonists xylazine and iodoclonidine had no effect at supramaximal concentrations. Prazosin, a specific alpha1-antagonist, reduced or eliminated the inhibition by Epi, but the response pattern suggests a low affinity. The alpha2-antagonist yohimbine, at concentrations </=0.3 micromol/l, had a minimal effect, but reduced the inhibition by Epi at concentrations of 1-10 micromol/l. This might indicate affinity to alpha1-adrenoceptors in amphibian skin. Activation of beta-adrenoceptors by isoproterenol (0.1-5 micromol/l) led to a transient increase of the baseline inactivated component of GCl with a slight reduction of the voltage-activated GCl at the higher concentrations, but the inhibitory effect of Epi was not altered. Epi, on the other hand, neither prevented nor reversed the induction of a voltage-insensitive GCl in toad skin caused by application of cAMP at supramaximal concentrations (>100 micromol/l CPT-cAMP). Preincubation of the serosal medium with Ca2+-free solution (in the presence of 2 mmol/l EGTA) for extended periods of time (>30 min) eliminated the response to Epi. It is concluded that alpha1-adrenoceptors participate in the physiological control of voltage-activated Cl- conductance in amphibian skin epithelium via modulation of intracellular Ca2+, presumably by efflux from intracellular stores.

1-Methyl-3-isobutylxanthine↗
PubMed2001

HCO3- potentiates the cAMP-dependent secretory response of the human distal colon through a DIDS-sensitive pathway.

We used the Ussing short-circuit technique to investigate the role of HCO3- in the adenosine 3',5'-cyclic monophosphate (cAMP)-dependent secretory response of the human distal colon. In HCO3(-)-free 4-(2-hydroxyethyl)-1-piperazineethanesulphonic acid (HEPES)-Ringer's, forskolin (10 mumol l-1 mucosal and serosal) evoked a sustained increase in short-circuit current (Isc) (delta Isc = 24 +/- 3 microA cm-2, n = 57). However, this was only 25% of the forskolin-stimulated Isc response in HCO3(-)-Ringer's (delta Isc = 84 +/- 8 microA cm-2, n = 57). The reduced response to forskolin in HCO3(-)-free HEPES-Ringer's was not due to inhibition of the secretory mechanism by HEPES, as replacing HCO3- with a different buffer, N-tris[hydroxymethyl)methyl-2-aminoethanesulphonic acid (TES), had a similar effect and inclusion of HEPES in the HCO3(-)-Ringer's did not reduce the secretory response. Similarly, it was not due to an indirect modulation of electrogenic Cl- secretion, as the forskolin-stimulated bumetanide-sensitive Isc was comparable in the two Ringer's. Rather it was due to the activation of a HCO3(-)-dependent Isc which was inhibited by serosal 4,4'-diisothiocyano-stilbene-2,2'-disulphonate (DIDS). This DIDS-sensitive Isc was not inhibited by acetazolamide, but it was inhibited by the replacement of bathing solution Cl- with gluconate, suggesting a role for a Na(+)-dependent Cl-/HCO3- exchanger in the cAMP-dependent secretory response of the human distal colon.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗
PubMed2001

Fatty acids inhibit anion secretion in rat colon: apical and basolateral action sites.

Ca2+-dependent secretagogues evoke only a transient Cl- secretion in intestinal epithelia, although they induce a prolonged increase in the intracellular Ca2+ concentration, suggesting that they may exert an additional antisecretory action. In order to study the mechanism of this antisecretory effect, Cl- secretion, measured as the increase in short-circuit current (Isc), was evoked by carbachol in the absence and presence of different inhibitors. Neither a calmodulin antagonist, calmidazolium, nor different inhibitors of the nitric oxide (NO) pathway, i.e. Nomega-nitro-L-arginine (L-NNA) and Nomega-nitro-L-arginine methylester (L-NAME), affected the carbachol-induced Isc. However, inhibition of phospholipases A2 (PLA2) by quinacrine or arachidonyltrifluoromethyl ketone (AACOCF3) enhanced the Isc response evoked by carbachol, suggesting a role of fatty acids in the downregulation of anion secretion. Neither econazole, a cytochrome P450 inhibitor, nor nordihydroguaiaretic acid (NDGA), an inhibitor of lipoxygenases, mimicked the action of the PLA2 blockers. Conversely, short- or medium-chain fatty acids inhibited the carbachol- and forskolin-induced Isc with caprate (C10:0) being the most efficient water-soluble fatty acid. This fatty acid inhibited a Cl- current, which was driven across the apical membrane by a serosally to mucosally directed Cl- gradient after depolarization of the basolateral membrane. A second action site of fatty acids seems to be the basolateral membrane. After permeabilization of the apical membrane with the ionophore nystatin, a mucosally to serosally directed K+ gradient induced a K+ current, which was also inhibited by caprate. These results indicate that carbachol not only acts as a secretagogue but at the same time initializes downregulation by increasing the intracellular concentration of fatty acids, a mechanism limiting the resulting Cl- secretion.

Animals↗