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PubMed1980

Calcium dependence of serotonin-induced changes in rabbit ileal electrolyte transport.

These studies describe the calcium dependence of the serotonin-induced changes in active electrolyte transport in rabbit ileum in vitro. In the presence of a standard calcium concentration (1.2 mM) in the serosal bathing fluid, serosal serotonin caused a transient increase in short-circuit current and a prolonged decrease in net Na and Cl fluxes. Removing calcium from the serosal (no calcium plus 1 mM EGTA) but not the mucosal bathing fluid inhibited the serotoin-induced increase in ileal short-circuit current, and also completely blocked the serotonin effects on net Na and net Cl fluxes. This inhibition was rapidly reversed by readding calcium. Removing serosal calcium did not inhibit all active electrolyte transport processes, as the effect of a maximum concentration of theophylline (10 mM) was not altered. Similarly, d,l-verapamil, a calcium channel blocker, inhibited the serotonin-induced changes in short-circuit current and in net Na and net Cl fluxes, but did not alter the theophylline effects. In contrast, d-verapamil, a stereoisomer which does not block calcium channels, did not inhibit the serotonin-induced changes. The calcium dependence of these serotonin effects was associated with increased uptake of 45Ca into rabbit ileum, including increaed 45Ca uptake from the serosal surface. Serotonin also increased the rate of 45Ca efflux from rabbit ileum into a calcium-free solution, compatible with serotonin increasing the ileal plasma membrane permeability to calcium. It is postulated that serotonin affects active intestinal electrolyte transport by a mechanism dependent on serosal but not mucosal calcium that involves an increase in the intestinal plasma membrane permeability to calcium, and perhaps an increase in intracellular calcium.

Animals↗
PubMed1989

Characterization of aldosterone-induced potassium secretion in rat distal colon.

The role of apical and basolateral membranes in aldosterone-induced active potassium (K) secretion in rat distal colon was investigated by measuring mucosal-to-serosal (Jms) and serosal-to-mucosal (Jsm) 42K fluxes (mueq.h-1.cm-2) across isolated stripped mucosa under short-circuit conditions in normal and secondary-hyperaldosterone animals. In normal colons mucosal tetraethylammonium (TEA; 30 mM) or barium (Ba; 5 mM), but not cesium (Cs; 15 mM), reduced Jsm without affecting Jms. In aldosterone animals (a) net K secretion (-0.54 +/- 0.11) was converted to net K absorption (0.63 +/- 0.15) by mucosal TEA, which produced a marked reduction in Jsm (0.82 +/- 0.07) and an increase in Jms (0.35 +/- 0.07). In contrast mucosal Ba resulted in a relatively smaller reduction in JK(sm) without altering JK(ms), whereas mucosal Cs was ineffective; (b) serosal bumetanide or the removal of serosal Na or Cl markedly inhibited JK(sm and abolished net K secretion; and (c) serosal ouabain (1 mM) produced qualitatively similar effects to those of serosal bumetanide. These results demonstrate that (a) normal rat distal colon contains apical TEA- and Ba-sensitive K channels; (b) aldosterone induces TEA-sensitive and Ba-sensitive apical K channels; (c) aldosterone-induced K secretion requires both the Na,K-pump and Na-K-2Cl cotransport for K uptake across the basolateral membrane; and (d) alteration of any of these processes results in inhibition of aldosterone-induced active K secretion simultaneously with stimulation of K absorption.

Aldosterone↗
PubMed2002

Effect of colchicine and cytokines on MEFV expression and C5a inhibitor activity in human primary fibroblast cultures.

BACKGROUND: Familial Mediterranean fever is an autosomal recessive disease characterized by sporadic attacks of inflammation affecting the serosal spaces. The gene associated with FMF (MEFV), mainly expressed in neutrophils, was recently found to be expressed also in primary cultures of serosal origin (peritoneal and synovial fibroblasts). A C5a inhibitor, previously detected in normal serosal fluids, was recently identified in serosal cultures as well, and was found to be deficient in serosal fluids and cultures obtained from FMF patients. OBJECTIVE: To investigate the effect of colchicine (the main therapeutic agent for FMF patients) and certain inflammatory cytokines (IL-1 beta, TNF-alpha, IFN-alpha, IFN-gamma) on MEFV expression and C5a inhibitor activity in neutrophils and primary peritoneal fibroblast cultures. METHODS: Human primary peritoneal fibroblast cultures and neutrophils were studied for MEFV expression and C5a inhibitor activity, using reverse transcription-polymerase chain reaction and C5a-induced myeloperoxidase assay, respectively, in the presence and absence of colchicine and cytokines. RESULTS: MEFV expression in neutrophils was high and could not be induced further. Its expression in the peritoneal fibroblasts was lower than in neutrophils and could be induced using colchicine and cytokines parallel with induction of C5a inhibitor activity. Semi-quantitative RT-PCR assays enabled estimation of MEFV induction by the cytokines at 10-100-fold and could not be further increased by concomitant addition of colchicine. CONCLUSION: Serosal tissues, which are afflicted in FMF, express colchicine and cytokine-inducible MEFV and contain inducible C5a inhibitor activity. The relation between the ability of colchicine to induce MEFV and C5a inhibitor activity, and its efficacy in FMF treatment, require further investigation.

Antineoplastic Agents↗
PubMed2002

Effect of thoracic epidural anaesthesia on colonic blood flow.

BACKGROUND: The effect of thoracic epidural block on splanchnic blood flow is unclear. It remains to be resolved if sympathetic block, increases or decreases regional splanchnic blood flow and whether regional splanchnic flow becomes dependent on cardiac output or perfusion pressure. A clear understanding of the regional haemodynamic consequences of an epidural block may modify practice with respect to epidural anaesthesia. METHODS: Fifteen patients, who underwent anterior resection for rectal cancer, had invasive intraoperative monitoring of arterial pressure, central venous pressure, cardiac output, inferior mesenteric artery flow (Doppler flow probe), and colonic serosal red cell flux (laser Doppler probe), while an epidural block was established with local anaesthetic. In three consecutive time periods, arterial pressure was first allowed to fall (to a mean arterial pressure of 60 mm Hg), then treated with colloid fluid resuscitation and finally by vasopressors until the pre-epidural arterial pressure had been restored. RESULTS: On induction of epidural block, there was a reduction in mean colonic serosal red cell flux to 65% and inferior mesenteric artery flow to 80% (mean) of pre-epidural levels. There was a strong association between mean arterial pressure and both measured inferior mesenteric artery blood flow (P < 0.004) and colonic serosal red cell flux (P < 0.0001). Changes in cardiac output were poorly associated with either inferior mesenteric artery blood flow (P = 0.638) or colonic serosal red cell flux (P = 0.265). Inferior mesenteric artery blood flow and colonic serosal red cell flux were restored to pre-epidural levels after arterial pressure had been improved with a vasopressor. CONCLUSION: Once intraoperative epidural block has been established, colonic serosal red cell flux and inferior mesenteric artery flow are more closely associated with changes in mean arterial pressure than changes in cardiac output. The measured reduction in colonic flow does not respond to an increase in cardiac output with fluid resuscitation, but requires the use of a vasopressor to increase arterial pressure, before colonic blood flow is improved.

Aged↗
PubMed1989

Coupling of volume and Na+ transport in frog skin epithelium.

Whole skins and isolated epithelia were bathed with isotonic media (congruent to 244 mOsm) containing sucrose or glucose. The serosal osmolality was intermittently reduced (congruent to 137 mOsm) by removing the nonelectrolyte. Transepithelial and intracellular electrophysiological parameters were monitored while serosal osmolality was changed. Serosal hypotonicity increased the short-circuit current (ISC) and the basolateral conductance, hyperpolarized the apical membrane (psi mc), and increased the intracellular Na+ concentration. The increases in apical conductance and apical Na+ permeability (measured from Goldman fits of the relationship between amiloride-sensitive current and psi mc) were not statistically significant. To verify that the osmotically induced changes in ISC were mediated primarily at the basolateral membrane, the basolateral membrane potential of the experimental area was clamped close to 0 mV by replacing the serosal Na+ with K+ in Cl--free media. The adjoining control area was exposed to serosal Na+. Serosal hypotonicity produced a sustained stimulation of ISC across the control, but not across the adjoining depolarized tissue area. The current results support the concept that hypotonic cell swelling increases Na+ transport across frog skin epithelium by increasing the basolateral K+ permeability, hyperpolarizing the apical membrane, and increasing the electrical driving force for apical Na+ entry.

Amiloride↗
PubMed1984

Effect of Senokot on rat intestinal electrolyte transport. Evidence of Ca++ dependence.

The mechanism of action of Senokot, a widely used laxative, has not been established. Senokot was given orally to rats 8-14 h before intestinal water and electrolyte transport were studied. Senokot significantly decreased colonic and jejunal water absorption measured in vivo by the single-pass perfusion technique. The Senokot changes were not associated with changes in jejunal or colonic histology or adenylate cyclase activity or colonic cyclic adenosine monophosphate content. Senokot also altered active electrolyte transport in rat descending colon as measured by the Ussing chamber-voltage clamp technique. These changes consisted of an increase in short-circuit current and a decrease in active Na and Cl transport that was due to a decrease in the mucosal-to-serosal fluxes. The changes in active electrolyte transport were dependent on Ca++ in the serosal but not the mucosal bathing solution. In contrast, addition of 10(-4) M verapamil to the serosal surface did not alter the Senokot effect. In spite of a dependence on serosal Ca++, Senokot did not alter 45Ca++ entry across the colonic serosal surface. The phospholipase A2 inhibitor quinacrine (10(-4) M) also did not alter the effect of Senokot on colonic Na and Cl transport. Senokot alters active colonic Na and Cl transport via a presently unknown mechanism that is dependent on serosal Ca++.

Adenylyl Cyclases↗
PubMed1995

Transepithelial transport of short chain fatty acids and their metabolism in pig hindgut.

In vitro experiments in Ussing chambers were performed in order to study the transport as well as the intraepithelial metabolism of short chain fatty acids in the caecum, proximal and distal colon. Stripped epithelial tissues were incubated in isotonic buffer solutions. SCFA were only present in the mucosal solutions at a concentration of 60 mmol/l consisting of 60% acetate, 25% propionate and 15% butyrate at the beginning of each flux rate measurement. For osmotic reasons SCFA were completely replaced by gluconate in serosal buffer solutions. The tissues were incubated under short-circuit current conditions for 1 h. In addition, with epithelia from the proximal colon flux rate measurements were also performed after setting the transepithelial potential difference (PD) to 25 mV with the serosa being positive. At the end of each 1h flux period samples were taken from the mucosal and serosal solutions for HPLC analysis of SCFA concentrations. SCFA transport and rate of intraepithelial metabolism were calculated from mucosal uptake and serosal release during the experimental periods. In the presence of 2 cm2 serosal area of the tissues, mucosal SCFA uptake ranged between 53 and 75 mumol with no change of molar SCFA proportions irrespective of hindgut segment. Voltage clamp condition did not influence mucosal SCFA uptake indicating the presence of electroneutral transport mechanisms. Serosal SCFA release ranged between 105 and 126 mumol thus exceeding mucosal loss. In serosal solutions molar butyrate proportions were significantly lower in comparison with mucosal solutions. This was accompanied by slight increases of molar acetate proportions indicating intraepithelial butyrate cleavage.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1997

Evidence of basolateral water permeability regulation in amphibian urinary bladder.

It is well known that arginine vasopressin (AVP) produces up to a 40-fold increase (0.1 to 4.0 microL/min.cm2) in net water flux across the amphibian urinary bladder under an osmotic gradient (mucosal side 10% hypotonic). No AVP effect is observed when the gradient is in the opposite direction (serosal hypotonic). Similar asymmetrical behavior to osmotic gradients occurs in the frog corneal epithelium. This rectification phenomenon has not been satisfactorily explained. We measured net water fluxes in bladder sacs and confirmed that AVP has no effect when the serosal bath is hypotonic. We reasoned that the 'abnormal' serosal osmolarity was inducing changes in membrane water permeability, the very parameter being measured. Thus, we studied the effect of solution osmolarity on diffusional water flow (Jdw) across the frog bladder using 3H2O. As expected, AVP doubled Jdw (in either direction from 12 to 21 microL/min.cm2) when the serosal solution was iso-osmolar regardless of mucosal osmolarity. However, in the AVP-stimulated bladders, hypo-osmolarity of the serosal solution reduced Jdw by 42%, an effect that was reversible when normal osmolarity was re-established. Amphotericin B (instead of AVP) was used to irreversibly increase the permeability to water of the apical membrane. Under these conditions, basolateral hypotonicity also reversibly decreased Jdw by 32%, suggesting the basolateral membrane as the site where permeability is reduced. SEM and TEM of the tissue shows extreme swelling when it was exposed to serosal hypotonicity with or without AVP and typical surface morphology changes following hormone stimulation. We conclude that this swelling may initiate a signaling mechanism that reduces basolateral water permeability. These findings constitute evidence of basolateral water channel permeability regulation, which can also contribute to cell volume regulation.

Amphibian Proteins↗
PubMedDate not supplied

Recurrent episodic fever. A presenting feature of familial Mediterranean fever.

OBJECTIVES: To study the natural course and outcome of recurrent episodic fever without serositis as a presenting feature of familial Mediterranean fever (FMF). PATIENTS: Of 309 children with FMF seen over a period of 5 years, 8 presented with recurrent episodes of fever without serositis, imposing a difficult diagnostic problem. RESULTS: The age at onset of fever ranged between 5 months and 8 years with a mean of 2.5 years. Five patients eventually developed serositis. The duration between onset of fever and onset of serositis ranged between 1.5-3 years with a mean of 2 years. Of the 3 patients who did not develop serositis, 2 had a family history of FMF. Therapeutic response to colchicine was dramatic in 7 children (one refused colchicine prophylaxis). CONCLUSION: Episodic fever alone without serositis is a presenting feature of FMF. In patients from Mediterranean ancestors and/or the presence of family history of FMF, a therapeutic diagnostic test with colchicine could be rewarding.

Age of Onset↗
PubMed2001

Embryogenesis of the dipluran Lepidocampa weberi Oudemans (hexapoda: diplura, campodeidae): formation of dorsal organ and related phenomena.

The developmental changes of embryonic membranes of a dipluran Lepidocampa weberi, with special reference to dorsal organ formation, are described in detail by light, scanning, and transmission electron microscopies. Newly differentiated germ band and serosa secrete the blastodermic cuticle at the entire egg surface beneath the chorion. Soon after, the serosal cells start to move dorsad. All the serosal cells finally concentrate at the dorsal side of the egg and form the dorsal organ. During their concentration, the serosal cells attenuate their cytoplasm to form filaments. The extensive area from which the serosa has receded is occupied by a second embryonic membrane, the amnion, which originates from the embryonic margin. The embryo and newly emerged amnion then secrete three fine cuticular layers, "cuticular lamellae I, II, and III," above which the filaments of the (developing) dorsal organ are situated. With the progression of definitive dorsal closure, the amnion reduces its extension, the dorsal organ is incorporated into the body cavity of the embryo, and the amnion and dorsal organ finally degenerate. The dorsal organ of diplurans is formed by the concentration of whole serosal cells, while that of collembolans is formed by the direct differentiation of a part of serosal cells. However, the dorsal organs of diplurans and collembolans closely resemble each other in major aspects, including that of ultrastructural features, and there is no doubt regarding their homology. The amnion, which has been regarded as being a characteristic of Ectognatha, also develops in the Diplura. This might suggest a closer affinity between the Diplura and Ectognatha than previously believed.

Animals↗
PubMed1993

Prognostic value of the number of metastatic lymph nodes in gastric cancer with radical surgery.

To evaluate the effectiveness of extended lymph node dissection in gastric cancer, the relationship between the number of lymph nodes with metastasis and the long-term outcome was studied retrospectively in 761 patients who underwent curative resection with extensive lymph node dissection. The cumulative 5-year survival rate was 85.8% in patients without lymph node metastasis, 60.2% in those with 1-4 lymph nodes, 35.6% with 5-10 nodes, and 12.3% with 11 or more nodes involved. Concerning N2 or N3 patients in whom metastatic lymph nodes would have remained without extensive dissection, the 5-year survival rate was 70.5% in those with 1-4 lymph nodes involved and 44.0% with 5 or more lymph nodes involved when no serosal invasion was observed. It was 38.5% with 1-4 lymph nodes and 5% with 5 or more lymph nodes involved when serosal invasion was observed. These results suggest that extensive lymph node dissection is effective in gastric cancer patients without serosal invasion and, when only a few lymph nodes are involved, also in those with serosal invasion. However, it is not considered to be effective in patients with serosal invasion and metastasis to many lymph nodes. Combination therapies are thought to be required in such patients.

Adult↗
PubMed2002

Serum, pleural effusion, and ascites CA-125 levels in ovarian cancer and nonovarian benign and malignant diseases: a comparative study.

OBJECTIVES: Cancer antigen-125 (CA-125) is not a specific tumor marker and it is synthesized by normal and malignant cells of different origins. Recently it has been shown that various diseases are associated with increased CA-125 levels, especially in the presence of serosal fluid. The aim of this study is to investigate serum and fluid CA-125 levels in patients with different diseases. METHODS: A total of 133 patients and 23 healthy control cases were included in the study and divided into eight groups on the basis of disease and the presence of fluid in the serosal cavities. Serum and serosal fluid CA-125 levels were measured by a commercial enzyme immunoassay kit at the same time. Comparisons among the groups were made. RESULTS: Abnormal levels of serum CA-125 were observed in 76% of ovarian cancer patients; 96% in patients with ascites and 56% in patients without ascites. Moreover, elevated serum CA-125 levels were detected in 52% of patients with hepatic diseases, in 100% of patients with nongynecologic peritoneal carcinomatosis, and in 87% of patients with pleural effusion. Serum and fluid CA-125 levels were significantly higher in cases of ovarian cancer with ascites than in the other groups (P < 0.01). A positive correlation between serum CA-125 levels and ascites amounts was observed in cases of ovarian cancer with ascites (P < 0.01, r = 0.81). Furthermore, no correlation was observed between ovarian mass volume and serum CA-125 levels in ovarian cancer patients with stage I disease without ascites (P = 0.08, r = 0.48). CONCLUSIONS: Although CA-125 levels may be considered a sensitive tumor marker in patients with epithelial ovarian cancer, it was determined that high serum CA-125 levels were closely related to the presence of serosal fluids and serosal involvement, whatever the origin is. These results should be considered in the interpretation of CA-125 elevation in patients with ovarian cancer.

Adult↗
PubMed1992

AlF4- and vanadate stimulate chloride secretion in rabbit colon by a Ca(2+)-dependent mechanism.

Stripped rabbit descending colon mucosae were studied in vitro in modified Ussing chambers to determine the effects of AlF4- and vanadate on Cl- transport. Serosal additions of AlF4- and vanadate increase short circuit current (Isc) and tissue conductance, while luminal addition of the agents is ineffective. Addition of aluminium potentiates the effect of NaF on Isc. AlF4- and vanadate increase serosal-to-mucosal flux of 36Cl without affecting mucosal-to-serosal flux. The effects of these agents on Isc are markedly inhibited by serosal addition of bumetanide and depend on the presence of Na+ in the serosal bathing solution. The effects of AlF4- and vanadate on Isc are dependent on the presence of Ca2+ in the bathing solution, and are completely inhibited by indomethacin, but the effect of forskolin is not affected by the removal of Ca2+ from the bathing solution and the addition of indomethacin. AlF4- and vanadate significantly increase the level of inositol phosphate metabolites. The results indicate that AlF4- and vanadate increase Cl- secretion in the rabbit colon via an increase in prostaglandin synthesis which is mediated by the increase of intracellular Ca2+ concentrations.

Aluminum↗
PubMed1985

Effects of anions on cellular volume and transepithelial Na+ transport across toad urinary bladder.

The effects of complete substitution of gluconate for mucosal and/or serosal medium Cl- on transepithelial Na+ transport have been studied using toad urinary bladder. With mucosal gluconate, transepithelial potential difference (VT) decreased rapidly, transepithelial resistance (RT) increased, and calculated short-circuit current (Isc) decreased. Calculated ENa was unaffected, indicating that the inhibition of Na+ transport was a consequence of a decreased apical membrane Na+ conductance. This conclusion was supported by the finding that a higher amiloride concentration was required to inhibit the residual transport. With serosal gluconate VT decreased, RT increased and Isc fell to a new steady-state value following an initial and variable transient increase in transport. Epithelial cells were shrunken markedly as judged histologically. Calculated ENa fell substantially (from 130 to 68 mV on average). Ba2+ (3 mM) reduced calculated ENa in Cl- Ringer's but not in gluconate Ringer's. With replacement of serosal Cl- by acetate, transepithelial transport was stimulated, the decrease in cellular volume was prevented and ENa did not fall. Replacement of serosal isosmotic Cl- medium by a hypo-osmotic gluconate medium (one-half normal) also prevented cell shrinkage and did not result in inhibition of Na+ transport. Thus the inhibition of Na+ transport can be correlated with changes in cell volume rather than with the change in Cl-per se. Nystatin virtually abolished the resistance of the apical plasma membrane as judged by measurement of tissue capacitance. With K+ gluconate mucosa, Na+ gluconate serosa, calculated basolateral membrane resistance was much greater, estimated basolateral emf was much lower, and the Na+/K+ basolateral permeability ratio was much higher than with acetate media. It is concluded the decrease in cellular volume associated with substitution of serosal gluconate for Cl results in a loss of highly specific Ba2+-sensitive K+ conductance channels from the basolateral plasma membrane. It is possible that the number of Na+ pump sites in this membrane is also decreased.

Animals↗
PubMed1987

An amiloride-sensitive Na+ conductance in the basolateral membrane of toad urinary bladder.

Exposing the apical membrane of toad urinary bladder to the ionophore nystatin lowers its resistance to less than 100 omega cm2. The basolateral membrane can then be studied by means of transepithelial measurements. If the mucosal solution contains more than 5 mM Na+, and serosal Na+ is substituted by K+, Cs+, or N-methyl-D-glucamine, the basolateral membrane expresses what appears to be a large Na+ conductance, passing strong currents out of the cell. This pathway is insensitive to ouabain or vanadate and does not require serosal or mucosal Ca2+. In Cl-free SO2-(4) Ringer's solution it is the major conductive pathway in the basolateral membrane even though the serosal side has 60 mM K+. This pathway can be blocked by serosal amiloride (Ki = 13.1 microM) or serosal Na+ ions (Ki approximately 10 to 20 mM). It also conducts Li+ and shows a voltage-dependent relaxation with characteristic rates of 10 to 20 rad sec-1 at 0 mV.

Amiloride↗
PubMed1999

Histopathologic characteristics of colorectal cancer with liver metastasis.

PURPOSE: Although prognostic factors of colorectal cancer have been studied, factors associated with liver metastasis have not been fully investigated. The aim of this study was to clarify the histopathologic characteristics of colorectal cancer with liver metastasis. METHODS: We performed a retrospective histopathologic study on 335 patients who underwent resection of colorectal cancer during 15 years. Histopathologic parameters of tumors with liver metastasis were compared with those without liver metastasis. RESULTS: Forty-one patients (12 percent) had simultaneous liver metastasis. Tumors having liver metastasis, when compared with those not having liver metastasis, were characterized by high frequency of tumor size more than 6 cm (51 vs. 28 percent; P < 0.01), presence of serosal invasion (98 vs. 66 percent; P < 0.01), lymphatic invasion (34 vs. 15 percent; P < 0.01), venous invasion (24 vs. 3 percent; P < 0.01), and lymph node metastasis (85 vs. 39 percent; P < 0.01). Multivariate analysis showed that factors independently associated with liver metastasis were serosal invasion, venous invasion, and lymph node metastasis. Accuracy in the diagnosis of liver metastasis was highest for venous invasion (88 percent) and lowest for serosal invasion (41 percent). Among 98 patients with both serosal invasion and lymph node metastasis, tumors with and without liver metastasis were different in frequency of venous invasion (26 vs. 6 percent; P < 0.01) and extracolic lymph node metastasis (68 vs. 47 percent; P < 0.05). CONCLUSION: In colorectal cancer important factors associated with liver metastasis were serosal invasion, venous invasion, and lymph node metastasis. Significant determinants for liver metastasis from colorectal cancer were venous invasion and extracolic lymph node metastasis.

Adenocarcinoma↗
PubMed2003

Histamine-induced chloride secretion is mediated via H2-receptors in the pig proximal colon.

OBJECTIVE: The aim of this study was to investigate the action of histamine on function of epithelia in the pig proximal colon. MATERIAL AND METHODS: Isolated epithelia of the pig proximal colon were prepared by slide-stripping and mounted in Ussing chambers. Short-circuit current (Isc) was measured after serosal addition of histamine (20 micromol/l) with or without pretreatment with histamine receptor antagonists (H1: chlorpyramine, 10 micromol/l; H2: famotidine, 100 micromol/l; H3: thioperamide, 10 micromol/l), a cyclooxygenase inhibitor (indomethacin, 10 micromol/l), or a neuronal conduction blocker (tetrodotoxin, 1 micromol/l). Alternatively, histamine receptor agonists (H1: 2-pyridylethylamine; H2: dimaprit; H3: R-alpha-methylhistamine, each 100 micromol/l) were added to the serosal side. Flux studies using 14C-mannitol, 22Na+ and 36Cl- were performed in the presence of 100 micromol/l histamine on the serosal side. RESULTS: Serosal application of histamine induced a rapid rise in Isc with a maximum 3 min after addition, followed by a slow decrease. Only pretreatment with famotidine decreased the epithelial response to histamine. Pretreatments with chlorpyramine, thioperamide, indomethacin or tetrodotoxin did not change histamine-induced increases in Isc. Action of histamine could be simulated by dimaprit, but not by 2-pyridylethylamine or R-alpha-methylhistamine. Histamine induced an increase in serosal-to-mucosal chloride flux leading to a decrease of chloride net absorption. Fluxes of sodium and mannitol were not affected by histamine. CONCLUSIONS: In contrast to the importance of H1-receptors in other gut epithelia, histamine acts directly via H2-receptors in the porcine proximal colon. Changes in Isc after histamine addition are primarily due to chloride secretion. The paracellular permeability is not influenced by histamine.

Animals↗
PubMed2000

Effects of medium hypertonicity on water permeability in the mammalian rectum: ultrastructural and molecular correlates.

Minute-by-minute net water fluxes (Jw) were measured across the isolated rectal epithelium in rats and rabbits. Five minutes after a serosal (but not mucosal) hypertonic challenge (plus 200 mosmol/l) a significant increase in the basal Jw was recorded in both species [deltaJw, microl min(-1) cm(-2): 0.40+/-0.06 (rats); 0.45+/-0.10 (rabbits)]. At the same time, most epithelial cells shrank markedly while the intercellular spaces were wide open (electron microscopy studies). In freeze-fracture studies multi-strand tight-junction structures (only slightly modified by serosal hypertonicity in rabbits) were observed in control conditions. No structural changes were observed after mucosal hypertonicity (both in rats and rabbits). Immunohistochemical studies showed the expression of aquaporin 3 (AQP3) at the basolateral membrane of epithelial cells in the rat. A first conclusion is that the epithelium of the mammalian rectum is a highly polarized, aquaporin-3-containing, water permeability structure. The Jw increase induced by serosal hypertonicity was sensitive to mercurial agents in both species and no changes in unidirectional [14C]mannitol fluxes (Ps) or transepithelial resistance (RT) were observed during this Jw increase. These observations suggest a transcellular route for the osmotically induced increase in water fluxes. In the rabbit rectum the initial Jw response, associated with serosal hypertonicity, was a transient one. It was followed by a second, slow and HgCl2-sensitive Jw increase (a transient peak in paracellular mannitol permeability was also observed). A second conclusion is that serosal hypertonicity induces an increase in transcellular water permeability in both rat and rabbit rectum.

Animals↗