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PubMed2003

Detection of gastric slow wave uncoupling from multi-channel electrogastrogram: validations and applications.

Current methodology of single channel electrogastrography is unable to detect coupling or uncoupling of gastric slow waves, which is crucial for gastric emptying. In this study, a new methodology, called cross-spectral analysis method, was established to compute the coupling percentage of multi-channel gastric slow waves recorded using serosal electrodes and electrogastrogram (EGG). Two experiments were performed to validate the method and demonstrate its applications in clinical research. In experiment 1, simultaneous recordings of gastric slow waves were made in five dogs from serosal electrodes and cutaneous electrodes. In experiment 2, four-channel fasting EGGs were made in 10 volunteers for 30 min during waking and 30 min during non-rapid eye movement (REM) sleep. The validation study (experiment 1) showed that the slow wave coupling calculated from the EGGs was correlated with that computed from the serosal recordings. The gastric slow wave coupling percentages detected from both serosal and cutaneous recordings were significantly impaired during vasopressin infusion (6.3 +/- 2.6 vs 62.4 +/- 6.3, P < 0.001 for serosal recordings; 6.7 +/- 3.0 vs 57.2 +/- 2.7, P < 0.001 for cutaneous recordings), and the coupling percentages respectively calculated from serosal and cutaneous recordings were significantly correlated during the baseline recording period (R = 0.922, P < 0.05) and vasopressin infusion period (R = 0.916, P < 0.05). In experiment 2, the gastric slow wave became less coupled when healthy volunteers fell asleep. The percentage of slow wave coupling calculated from the EGGs was 68.2 +/- 17.9% during waking but 41.9 +/- 20.8 during non-REM sleep (P < 0.05). The method developed in this study is reliable for the detection of slow wave uncoupling from multi-channel EGGs. Gastric slow wave coupling is impaired during vasopressin infusion and sleep. These data suggest that this method has potential applications in physiological and clinical studies.

Adult↗
PubMed2005

Inhibitory effects of dietary calcium on the initial uptake and subsequent retention of heme and nonheme iron in humans: comparisons using an intestinal lavage method.

BACKGROUND: Calcium is the only reported dietary inhibitor of both heme- and nonheme-iron absorption. It has been proposed that the 2 forms of iron enter a common pool in the enterocyte and that calcium inhibits the serosal transfer of iron into blood. OBJECTIVES: We aimed to ascertain whether the inhibitory effect of calcium occurs during initial mucosal uptake or during serosal transfer and to compare the serosal transfer of heme and nonheme iron, which should not differ if the 2 forms have entered a common mucosal iron pool. DESIGN: Whole-gut lavage and whole-body counting were used to measure the initial uptake (8 h) and retention (2 wk) of heme and nonheme iron with and without a calcium supplement (450 mg). Two experiments tested basal meals with low iron bioavailability and 360 mg Ca (n = 15) or with high iron bioavailability and 60 mg Ca (n = 12). RESULTS: Added calcium reduced the initial uptake of heme iron by 20%, from 49% to approximately 40% from both meals (P = 0.02), and reduced the total iron absorbed from the low- and high-bioavailability meals by approximately 25% [from 0.033 to 0.025 mg (P = 0.06) and from 0.55 to 0.40 mg (P < 0.01), respectively]. Calcium did not affect the serosal transfer of either form of iron. CONCLUSIONS: Calcium supplementation reduced heme and total iron without significantly affecting nonheme-iron absorption, regardless of meal bioavailability. Calcium inhibited the initial mucosal uptake rather than the serosal transfer of heme iron. Differences in serosal transfer indicate that heme and nonheme iron did not enter a common absorptive pool within 8 h after a meal.

Administration, Oral↗
PubMed1982

Cholinergic agonists induce vectorial release of serotonin from duodenal enterochromaffin cells.

Serotonin-containing enterochromaffin cells in the rabbit duodenal mucosa span the tissue contacting both the luminal and serosal sides. When the serosal surface is stimulated with carbachol in vitro, serotonin is secreted on the serosal side but not the mucosal side. Carbachol added to the luminal side is ineffective. Atropine but not hexamethonium blocks the effect of carbachol. Acetylcholine on the serosal surface also stimulates serotonin release on the serosal side. These findings indicate that enterochromaffin cells possess on their serosal surfaces muscarinic receptors that mediate vectorial release of serotonin when activated by cholinergic agonists.

Acetylcholine↗
PubMed1989

Basolateral impalement of intestinal villus cells: electrophysiology of Cl- transport.

A method of dissecting the serosal muscle layers is described that transforms the villus of isolated Amphiuma small intestine into a flat sheet one cell layer thick, allowing rapid equilibration of the serosal medium with the basolateral membrane of the villus tip cells and direct access of the basal membrane to microelectrodes. The "villus sheet" preparation was used to examine the luminal and basolateral mechanisms of Cl- transport. The serosal membrane potential (Vs), measured with conventional microelectrodes, averaged -79.7 mV in tissues bathed in Cl- -free medium; the mucosal membrane potential (Vm) averaged -80.9 mV. Fractional resistance measured directly was 0.82 and 0.14 for the mucosal and serosal membranes, respectively. Elevation of bath [K] reduced Vm and Vs by 30.3 and 44.5 mV, respectively. Cl- (20 mM) added to the luminal medium reduced Vm by 23.9 mV and stimulated Cl- transport; luminal addition of furosemide then increased Vm by 5.6 mV and reduced Cl- transport. Addition of Cl- (20 mM) to the Cl- -free serosal fluid increased Vs 2.0 +/- 1.9 mV. On reducing the serosal [Cl] 10-fold Vs decreased 2.0 +/- 2.2 mV. These and other results indicate that basolateral Cl- exit is not over a conductive pathway. The villus sheet affords new opportunities for studying enterocyte function in the intact mucosa.

4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulfo↗
PubMed1996

Regulation of colonic ion transport by GRP. II. GRP modulates the epithelial response to PGE2.

The purpose of this study was to examine the potential modulatory effects of gastrin-releasing peptide (GRP) on prostaglandin (PG) E2-stimulated electrolyte transport across the distal colon epithelium. In an earlier study, PGE2 was shown to reduce net Cl absorption without altering the serosal-to-mucosal unidirectional Cl flux in porcine distal colon (19). In the present study, tissues were pretreated with serosal or mucosal GRP and subsequently stimulated with PGE2. The resulting increase in short-circuit current (ISC) was 152% (serosal GRP) and 49% (mucosal GRP) greater than control PGE2 responses alone. Serosal, but not mucosal, GRP also enhanced the ISC response to vasoactive intestinal peptide. On the basis of flux measurements, the combined effects of serosal GRP and PGE2 resulted in the activation of a transcellular pathway for Cl secretion, which was not activated by either mediator alone. The time course of the PGE2 response was also affected by GRP. Serosal GRP shortened the time to maximum ISC by 35%, whereas mucosal peptide lengthened the time to maximum ISC by 68% These results suggest that GRP acts as a modulator of PG action on electrolyte transport in the distal colon.

Animals↗
PubMed1997

cAMP-dependent sulfate secretion by the rabbit distal colon: a comparison with electrogenic chloride secretion.

The ability of a Cl-secreting epithelium to support net secretion of an anion other than a halide was investigated with 35SO4 flux measurements across the isolated, short-circuited rabbit distal colon. In most experiments, 36Cl fluxes were simultaneously measured to validate the secretory capacity of the tissues. Serosal addition of dibutyryl adenosine 3',5'-cyclic monophosphate (DBcAMP, 0.5 mM) stimulated a sustained net secretion of SO4 (about -3.0 nmol.cm-2.h-1 from a 0.20 mM solution) via an increase in the serosal-to-mucosal unidirectional flux, whereas Ca ionophore A-23187 (1 microM, serosal) produced a more transient stimulation of SO4 and Cl secretion. Net adenosine 3',5'-cyclic monophosphate (cAMP)-dependent SO4 and Cl secretion were strongly voltage sensitive, principally through the potential dependence of the serosal-to-mucosal fluxes, indicating an electrogenic transport process. Symmetrical replacement of either Na, K, or Cl inhibited cAMP-dependent SO4 secretion, whereas HCO3-free buffers had no effect on SO4 secretion. Serosal bumetanide (50 microM) or furosemide (100 microM) reduced DBcAMP-stimulated SO4 and Cl secretion, whereas serosal 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid or 4-acetamido-4'-isothiocyanostilbene-2,2'-disulfonic acid (50 microM) blocked DBcAMP-induced SO4 secretion while enhancing net Cl secretion and short-circuit current. Mucosal 5-nitro-2-(3-phenylpropylamino)benzoic acid partially inhibited SO4 secretion and completely inhibited Cl secretion. It is concluded that secretagogue-stimulated SO4 secretion, like Cl secretion, may be an electrogenic process mediated by diffusive efflux through an apical anion conductance. Cellular accumulation of SO4 across the basolateral membrane appears to be achieved by a mechanism that is distinct from that employed by Cl.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗
PubMed2002

Chloride transport in rabbit esophageal epithelial cells.

We investigated Cl(-) transport pathways in the apical and basolateral membranes of rabbit esophageal epithelial cells (EEC) using conventional and ion-selective microelectrodes. Intact sections of esophageal epithelium were mounted serosal or luminal side up in a modified Ussing chamber, where transepithelial potential difference and transepithelial resistance could be determined. Microelectrodes were used to measure intracellular Cl(-) activity (a), basolateral or apical membrane potentials (V(mBL) or V(mC)), and the voltage divider ratio. When a basal cell was impaled, V(mBL) was -73 +/- 4.3 mV and a(i)(Cl) was 16.4 +/- 2.1 mM, which were similar in presence or absence of bicarbonate. Removal of serosal Cl(-) caused a transient depolarization of V(mBL) and a decrease in a(i)(Cl) of 6.5 +/- 0.9 mM. The depolarization and the rate of decrease of a(i)(Cl) were inhibited by approximately 60% in the presence of the Cl(-)-channel blocker flufenamate. Serosal bumetanide significantly decreased the rate of change of a(i)(Cl) on removal and readdition of serosal Cl(-). When a luminal cell was impaled, V(mC) was -65 +/- 3.6 mV and a was 16.3 +/- 2.2 mM. Removal of luminal Cl(-) depolarized V(mC) and decreased a by only 2.5 +/- 0.9 mM. Subsequent removal of Cl(-) from the serosal bath decreased a(i)(Cl) in the luminal cell by an additional 6.4 +/- 1.0 mM. A plot of V(mBL) measurements vs. log a(i)(Cl)/log a(o)(Cl) (a(o)(Cl) is the activity of Cl(-) in a luminal or serosal bath) yielded a straight line [slope (S) = 67.8 mV/decade of change in a(i)(Cl)/a(o)(Cl)]. In contrast, V(mC) correlated very poorly with log a/a (S = 18.9 mV/decade of change in a/a). These results indicate that 1) in rabbit EEC, a(i)(Cl) is higher than equilibrium across apical and basolateral membranes, and this process is independent of bicarbonate; 2) the basolateral cell membrane possesses a conductive Cl(-) pathway sensitive to flufenamate; and 3) the apical membrane has limited permeability to Cl(-), which is consistent with the limited capacity for transepithelial Cl(-) transport. Transport of Cl(-) at the basolateral membrane is likely the dominant pathway for regulation of intracellular Cl(-).

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗
PubMed1983

Sodium-dependent chloride secretion across rabbit descending colon.

Electrogenic, cAMP-mediated Cl secretion across rabbit descending colon in vitro is independent of the rate or presence of active Na absorption. Yet, several observations indicate that this process is Na dependent: a) Cl secretion requires the presence of Na in the serosal solution alone, b) the kinetics of Cl transport as a function of external Na concentration are virtually identical to the Cl concentration dependence, and c) exchange of cell Cl with isotopic Cl added to the serosal solution is inhibited by Na-free media and by addition of furosemide to the serosal solution; the diuretic also inhibits Cl secretion. These findings suggest that Cl entry into the secretory cells across the basolateral membrane is mediated by NaCl cotransport. Addition of ouabain to, or removal of K from, the serosal solution inhibits Cl secretion so that Na entering the secretory cell across the basolateral membrane may be returned to the serosal solution by the Na-K pump. Finally, increasing the K concentration of the serosal solution inhibits Cl secretion under short-circuit conditions. This appears to result from K-induced depolarization of the electrical potential difference across the apical membrane so that diffusional Cl exit from cell to mucosal solution is reduced.

Amiloride↗
PubMed1983

Dihydroxy bile salt-induced alterations in NaCl transport across the rabbit colon.

The effects of increasing mucosal or serosal concentrations (1-4 mM) of taurochenodeoxycholate (TCDC) on sodium chloride transport across the isolated, short-circuited rabbit colon were examined. Mucosal TCDC produced dose-related increases in tissue conductance (Gt) and the unidirectional fluxes of Na+ and Cl- and dose-related decreases in net NaCl absorption. At 4 mM mucosal TCDC, Gt was increased fivefold, net sodium flux (JNanet) was reduced 50%, and JClnet was abolished. Serosal TCDC also produced dose-dependent changes in permeability that were quantitatively different. Four millimolar serosal TCDC produced a 2.7-fold increase in Gt, abolished JNanet, and stimulated electrogenic Cl- secretion. TCDC-induced Cl- secretion was stimulated by 10(-5) M serosal TCDC, inhibited by serosal furosemide or ouabain, did not alter theophylline-induced secretion (and vice versa), and occurred in the absence of serosal Ca2+. It is suggested that 1) TCDC inhibition of sodium absorption is indirect (i.e., not simply due to a reduction in the activity of the Na "pump," since Cl- secretion persists during conditions that abolish JNanet) and 2) TCDC induces Cl- secretion by enhancing the activity of basolateral membrane adenylate cyclase.

Animals↗
PubMed1986

Evidence against luminal one-for-one Cl(-)-HCO-3 exchange in urodele small intestine.

The ratio of Cl- absorbed to HCO3- secreted by the in vitro small intestine of Amphiuma was measured using 36Cl and titration. The aim was to estimate the stoichiometry and thereby elucidate the underlying transport mechanisms. For every mole of HCO3- secreted 1.8 mol of Cl- underwent net absorption. Indirect measures of net Cl- absorption and HCO3- secretion were validated. Several known and putative Cl- transport inhibitors were examined for their ability to inhibit the anion transport events. Disulfonic stilbenes [4-acetamido-4'-isothiocyanostilbene-2',2'-disulfonic acid and 4,4'-diisothiocyano-2,2'-disulfonate stilbene (DIDS)] and the diuretics piretanide and furosemide inhibited the Cl- absorptive flux (JClm----s) and simultaneously the HCO3- secretory flux (JHCO3-). The diuretics acetazolamide and bumetanide also reduced JHCO3- and JClm----s, although the latter effect was not statistically significant. The ratio of inhibition, delta JClm----s/delta JHCO3-, varied from 1.2 to 1.8 for the different inhibitors. The presence of Cl(-)-HCO3- exchange at the serosal membrane was deduced from the reduction of JClm----s and JHCO3- by serosally added stilbenes, the reduction of Cl- absorption when serosal Cl- was replaced (reduced Cl(-)-Cl- exchange), inhibition of the secretory-to-mucosal Cl- flux by serosal stilbenes, and enhancement of JHCO3- when serosal medium HCO3- was elevated. Addition of DIDS to the mucosal medium did not alter the secretory flux. The observations are not consistent with one-for-one exchange of Cl- for HCO3- at the mucosal membrane. Other possible mechanisms including rheogenic Cl- uptake in parallel with electrodiffusional efflux of HCO3- are discussed. The observed coupling ratio is compatible with a one-for-one exchange of Cl- for HCO3- at the serosal membrane.

Animals↗
PubMed1993

Effects of ammonium ion and ammonia on function and morphology of in vitro frog gastric mucosa.

The effects of ammonium ion (NH+4) and ammonia (NH3) on function and morphology of gastric epithelial cells were studied in intact sheets of in vitro frog (Rana catesbeiana) gastric mucosa. Luminal 115 mM NH4Cl at luminal pH 8.0 (calculated [NH3] 2.7 mM), but not at 5.0 (calculated [NH3] 3 microM) induced 1) an increase in intracellular pH (pHi) in oxynticopeptic cells (OPC) and decreases in transmucosal potential difference (PD) and electrical resistance (R) in resting tissues, 2) a decrease in histamine-stimulated H+ secretion and an increase in H+ backdiffusion after removal of luminal NH4Cl, and 3) augmented acidification of OPC during luminal acidification. Serosal 30 mM NH4Cl at serosal pH 7.2 (calculated [NH3] 0.47 mM) induced 1) an increase in pHi in OPC and inhibition of the alkalinization of OPC after removal of ambient Cl-, 2) a decrease in PD associated with the increase in R and decrease in short-circuit current, effects attenuated by serosal 15 mM K+, accentuated by 0.2 mM Ba2+, and abolished by removal of ambient Cl-, 3) a sudden drop of PD in resting, but not in stimulated tissues, effects prevented by high serosal pH (7.8), serosal HCO3-, or removal of luminal Cl-, 4) a decrease in histamine-stimulated H+ secretion and an increase in H+ backdiffusion after removal of NH4Cl, and 5) augmented acidification of OPC during luminal acidification. These results suggest that 1) luminal NH3, but not NH+4, increases backdiffusion of H+ from the lumen to the mucosa, 2) serosal NH3 and/or NH+4 induces depolarization of OPC and decreases electrogenic Cl- transport, thereby attenuating the activity of the basolateral Cl(-)-HCO3- exchanger in OPC, and 3) both of these effects contribute to the augmented acidification of OPC during exposure to high luminal [H+].

Ammonia↗
PubMed1999

Nitric oxide inhibits potassium transport in the rat distal colon.

The effect of the nitric oxide (NO) pathway on K+ (measured using 86Rb) transport in adult rat distal colon was investigated in muscle-stripped segments of colons mounted in Ussing chambers. When added to the mucosal solution, the endogenous precursor of NO, L-arginine (30 mM), inhibited both mucosal-to-serosal and serosal-to-mucosal 86Rb fluxes and caused a prolonged decrease of short-circuit current (Isc). This effect was significantly reduced by the NO synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME) but not by D-NAME. Mucosal application of S-nitroso-N-acetyl-penicillamine (SNAP) inhibited mucosal-to-serosal 86Rb flux without affecting serosal-to-mucosal transport. Serosal addition of two different exogenous NO donors, sodium nitroprusside (0.1 mM) and SNAP (0.2 mM), decreased serosal-to-mucosal 86Rb flux, whereas Isc increased. The SNAP-induced decrease in 86Rb flux was abolished by 1H-(1,2,4)oxodiazolo(4,3-a)quinoxalin-1-one (0.2 mM), a selective inhibitor of NO-stimulated soluble guanylyl cyclase, and by methylene blue (0.01 mM). Addition of 8-bromo-cGMP (2 x 10(-4) M) in the presence of an inhibitor of cGMP-specific phosphodiesterase mimicked the effects of NO-donating compounds. This study provides evidence that NO inhibits K+ transport in the rat distal colon via a cGMP-dependent pathway. The effect on net K+ transport may depend on the side of NO action.

Animals↗
PubMed1990

Mechanisms of sodium and chloride transport across equine tracheal epithelium.

Equine tracheal epithelium, stripped of serosal muscle, mounted in Ussing chambers, and bathed in plasmalike Ringer solution generates a serosa-positive transepithelial potential of 10-22 mV and a short-circuit current (Isc) of 70-200 microA/cm2. Mucosal amiloride (10 microM) causes a 40-60% decrease in Isc and inhibits the net transepithelial Na flux by 95%. Substitution of Cl with gluconate resulted in a 30% decrease in basal Isc. Bicarbonate substitution with 20 mM N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid decreased the Isc by 21%. The Cl-dependent Isc was inhibited by serosal addition of 1 mM amiloride. Bicarbonate replacement or serosal amiloride (1 mM) inhibits the net Cl flux by 72 and 69%, respectively. Bicarbonate replacement significantly reduces the effects of serosal amiloride (1 mM) on Isc, indicating its effect is HCO3 dependent. Addition of 8-bromoadenosine 3',5'-cyclic monophosphate (8-BrcAMP; 100 microM) causes a 40% increase in Isc. This effect is inhibited by subsequent addition of 10 microM serosal bumetanide. Bumetanide (10 microM) reduces net Cl secretion following stimulation with 8-BrcAMP (100 microM). Serosal addition of BaCl2 (1 mM) causes a reduction in Isc equal to that following Cl replacement in the presence or absence of 100 microM cAMP. These results suggest that 1) Na absorption depends on amiloride-inhibitable Na channels in the apical membrane, 2) Cl influx across the basolateral membrane occurs by both a Na-H/Cl-HCO3 parallel exchange mechanism under basal conditions and by a bumetanide-sensitive Na-(K?)-Cl cotransport system under cAMP-stimulated conditions, and 3) basal and cAMP-stimulated Cl secretion depends on Ba-sensitive K channels in the basolateral membrane.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed2006

Parathyroid hormone-related protein regulates intestinal calcium transport in sea bream (Sparus auratus).

Parathyroid hormone-related protein (PTHrP) is a factor associated with normal development and physiology of the nervous, cardiovascular, immune, reproductive, and musculoskeletal systems in higher vertebrates. It also stimulates whole body calcium uptake in sea bream (Sparus auratus) larvae with an estimated 60% coming from intestinal uptake in seawater. The present study investigated the role of PTHrP in the intestinal calcium transport in the sea bream in vitro. Unidirectional mucosal-to-serosal and serosal-to-mucosal 45Ca fluxes were measured in vitro in duodenum, hindgut, and rectum mounted in Ussing chambers. In symmetric conditions with the same saline, bathing apical and basolateral sides of the preparation addition of piscine PTHrP 1-34 (6 nM) to the serosal surface resulted in an increase in mucosal to serosal calcium fluxes in duodenum and hindgut and a reduction in serosal to mucosal in the rectum, indicating that different mechanisms are responsive to PTHrP along the intestine. In control asymmetric conditions, with serosal normal and mucosal bathed with a saline similar in composition to the intestinal fluid, there was a net increase in calcium uptake in all regions. The addition of 6 nM PTHrP 1-34 increased net calcium uptake two- to threefold in all regions. The stimulatory effect of PTHrP on net intestinal calcium absorption is consistent with a hypercalcemic role for the hormone. The results support the view that PTHrP, alone or in conjunction with recently identified PTH-like peptides, counteracts in vivo the hypocalcemic effects of stanniocalcin.

Animals↗
PubMed1983

Intracellular pH, transepithelial pH gradients, and ADH-induced water channels.

Urinary bladders of frogs were exposed to a transepithelial proton and osmotic gradient (serosal pH 8.1, Tris or bicarbonate buffer; mucosal pH 5.8, unbuffered) while the alkalinization rate of the mucosal bath and the net water movement were simultaneously monitored. It was observed that 1) the mucosal alkalinization rate was dependent on serosal pH and buffer; 2) oxytocin increased the mucosal alkalinization rate only when serosal bicarbonate was employed, whereas the net water movement augmented both when serosal bicarbonate or Tris buffers were used; 3) amiloride did not modify the mucosal alkalinization rate either before or after oxytocin; 4) the increases in the mucosal alkalinization rate and in the net water movement induced by oxytocin (serosal bicarbonate) were negatively correlated. In other experiments intracellular pH (pHi) was estimated with the DMO distribution technique with the following results. 1) Oxytocin increased the pHi when either serosal bicarbonate or Tris buffers was used and even in the presence of a low mucosal pH (Tris buffer, pH 5.8). 2) Important cellular acidification was observed when CO2 was bubbled (to pH 5.8), whereas the hydrosmotic response to 8-bromo-cAMP was clearly inhibited. These results indicate that cellular alkalinization could play a pivotal role in action of ADH, show that ADH can modify the transepithelial pH equilibrium mechanism, and suggest that intracellular pH regulation and water permeability control can be linked regulatory processes.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1987

Cytosolic calcium and the action of vasopressin in toad urinary bladder.

The effects of experimental procedures believed to increase cytosolic calcium on basal and vasopressin-stimulated osmotic water flow and transepithelial sodium transport were examined in the toad urinary bladder. Exposure of isolated toad bladders to quinidine, calcium ionophores (A23187, X537A), or low-sodium or potassium-free serosal solutions resulted in a dose-dependent decrease in the hydrosmotic response to vasopressin or exogenous adenosine 3',5'-cyclic monophosphate (cAMP). The degree of inhibition of cAMP-induced water flow induced by low-sodium or potassium-free serosal bathing media varied, and in a similar manner, with the serosal calcium concentration. The effects of quinidine sulfate (2 X 10-4 M), X537A (2 X 10(-5) M), and low serosal sodium (20 mM), but not that of A23187 (10(-5) M), were readily reversible. Exposure to quinidine (4 X 10(-4) M), A23187 (10(-5) M), X537A (5 X 10(-6) M), or low serosal sodium (2 mM) also inhibited the basal short-circuit current (SCC). Vasopressin, 4-20 mU/ml, completely overcame the inhibition of the SCC induced by quinidine, A23187, or low serosal sodium, but a submaximal dose of hormone (4 mU/ml) failed to fully reverse the inhibitory effect of X537A, 5 X 10(-6) M. These results are consistent with the view that 1) a Na-Ca exchange process operates across the basolateral surface of the granular epithelial cells of the toad urinary bladder in vivo, and 2) the level of free calcium in the granular cell cytosol plays a modulatory role in the control of apical membrane water and sodium permeability by vasopressin, and in the regulation of the basal rate of transepithelial sodium transport.

Animals↗
PubMed1989

Steroid metabolism determines mineralocorticoid specificity in the toad bladder.

Edwards et al. (C. R. W. Edwards, P. M. Stewart, D. Burt, L. Brett, M. A. McIntyre, W. S. Sutanto, E. R. de Kloet, and C. Monder, Lancet 2: 986-989, 1988) proposed that 11 beta-hydroxysteroid-dehydrogenase (11 beta-OHSD) plays a key role in the kidney by converting glucocorticoids (cortisol or corticosterone), which display a high affinity for type 1 mineralocorticoid receptors, into their inactive metabolites (cortisone or 11-dehydroxy-corticosterone), thus preventing their illicit occupation of the receptor in the target cell for aldosterone. We have tested this hypothesis in the urinary bladder of Bufo marinus by measuring the sodium transport responses to aldosterone and corticosterone. Aldosterone (10 nM) on the serosal side elicited a quarter of the maximal increase in sodium transport. At the same concentration, corticosterone (10 nM, serosal side) was ineffective. Adding corticosterone (10 nM) on the mucosal side elicited a response equivalent to that of aldosterone, suggesting that corticosterone was inactivated in the serosal or underlying tissue of the toad bladder. Carbenoxolone (10 microM, serosal side), a potent inhibitor of 11 beta-OHSD, did not modify the base-line sodium transport. However, in the presence of carbenoxolone (10 microM, serosal side, 2 h pretreatment) corticosterone (10 nM, serosal side) became as potent as aldosterone in eliciting the mineralocorticoid response. Our data are consistent with the idea that corticosterone is converted into an inactive metabolite in the mucosal and/or submucosal tissue of the toad bladder. These studies are consistent with our concept that 11 beta-OHSD is crucial in protecting the nonspecific mineralocorticoid receptor from glucocorticoid.

11-beta-Hydroxysteroid Dehydrogenases↗
PubMed1999

Splanchnic hemodynamics and gut mucosal-arterial PCO(2) gradient during systemic hypocapnia.

The effects of hypocapnia [arterial PCO(2) (Pa(CO(2))) 15 Torr] on splanchnic hemodynamics and gut mucosal-arterial P(CO(2)) were studied in seven anesthetized ventilated dogs. Ileal mucosal and serosal blood flow were estimated by using laser Doppler flowmetry, mucosal PCO(2) was measured continuously by using capnometric recirculating gas tonometry, and serosal surface PO(2) was assessed by using a polarographic electrode. Hypocapnia was induced by removal of dead space and was maintained for 45 min, followed by 45 min of eucapnia. Mean Pa(CO(2)) at baseline was 38.1 +/- 1.1 (SE) Torr and decreased to 13.8 +/- 1.3 Torr after removal of dead space. Cardiac output and portal blood flow decreased significantly with hypocapnia. Similarly, mucosal and serosal blood flow decreased by 15 +/- 4 and by 34 +/- 7%, respectively. Also, an increase in the mucosal-arterial PCO(2) gradient of 10.7 Torr and a reduction in serosal PO(2) of 30 Torr were observed with hypocapnia (P < 0.01 for both). Hypocapnia caused ileal mucosal and serosal hypoperfusion, with redistribution of flow favoring the mucosa, accompanied by increased PCO(2) gradient and diminished serosal PO(2).

Alkalosis, Respiratory↗