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PubMed1996

Ion transport mechanisms in native rabbit nasal airway epithelium.

Net ion transports in rabbit nasal airway epithelium (RNAE) were estimated from unidirectional fluxes of 22Na+, 36Cl-, and 86Rb+ (K+ tracer), short-circuit current (Isc), and epithelial conductance (Gt) under short-circuit conditions in excised parallel RNAE from the two sides of the nasal septum mounted in Ussing chambers at 37 degrees C. Net Na+ absorption (JNa; 76 nmol.min-1.cm-2) was nearly equal to the net charge flux (Jnet), equivalent to the control Isc of 137 microA/cm2 (Jnet = Isc/zF = 85 neq.min-1.cm-2). Secretions of Cl- (9 nmol.min-1.cm-2) and K+ (Rb+) (1.2 nmol.min-1.cm-2) were small. Intra-animal variations between right- and left-side Isc values were small compared with large interanimal variations, suggesting long-term regulation of JNa. Serosal ouabain (10(-4) M) abolished Isc. Mucosal amiloride (10(-4) M) maximally inhibited Isc by 68% and JNa by 78%, abolished K+ (Rb+) secretion, increased Cl- secretion slightly (to 16 nmol.min-1.cm-2), and decreased control Gt (13.4 mS/cm2) by 26%. Amiloride-insensitive JNa was inhibited approximately 50% by mucosal hydrochlorothiazide (10(-4) M) but not by mucosal bumetanide, phloridzine, or ethoxzolamide. The Cl- secretion was abolished by serosal bumetanide (10(-4) M) and also by mucosal diphenylamine-2-carboxylate (2.5.10(-4) M) or bumetanide (10(-4) M). Serosal Ba2+ (2 mM) inhibited JNa and increased K+ (Rb+) secretion. The latter was blocked by mucosal Ba2+. Passive Cl- (but not Na+) fluxes varied proportionally with Gt and were approximately four times higher than passive Na+ fluxes, suggesting 1) significant anion selectivity of a low-resistance paracellular pathway and 2) separate routes for paracellular Cl- and Na+ fluxes. We conclude that RNAE is a suitable model organ for studies of regulation of JNa in native human airway epithelia.

Amiloride↗
PubMed1989

Organic anion and cation transport in crab urinary bladder.

Crab urinary bladder, a simple, flat-sheet epithelium, is structurally and functionally analogous to vertebrate renal proximal tubule. Like proximal tubule, crab bladder plays an important role in the excretion of potentially toxic, charged metabolites and xenobiotics. Bladders from Cancer borealis secrete monovalent, organic anions and cations in vivo and in vitro. For organic cations, secretion is a two-step process, with mediated and energetically downhill uptake into cells at the serosal membrane and uphill exit at the luminal membrane. The uptake step may be driven by the electrical potential difference across the serosal membrane, the luminal step by organic cation-proton exchange. Monovalent organic anions are also secreted by a separate two-step process. Recent experiments with intact bladder tissue and isolated membrane vesicles show that (as in mammalian proximal tubule) uphill serosal uptake can be coupled indirectly to the Na+ gradient. Organic anion (p-aminohippurate; PAH) uptake is driven by exchange for certain divalent organic anions, e.g., glutarate and alpha-ketoglutarate. The divalent anion gradient (in greater than out) is in turn maintained by Na+-coupled divalent uptake. The PAH exist step at the luminal membrane is mediated and downhill; it may involve anion exchange.

Animals↗
PubMed1997

Bicarbonate and CO2 transport across the skin of the leopard frog, Rana pipiens: effect of PGF2alpha.

The amphibian skin represents an important organ for osmoregulation and, like the mammalian kidney, maintains acid-base balance by secreting protons or base. However, the lack of a reliable and accurate method to measure the contribution of unidirectional fluxes of HCO3- ions to this mechanism has been an obstacle for the determination of the role of bicarbonate in epithelial acid-base homeostasis. Recently, one of us developed a method that allows for the reliable determination of transepithelial fluxes of bicarbonate, and this method was applied to determine unidirectional fluxes of (14)CO2 and H(14)CO3 under a variety of conditions. We report that the combined CO2 and HCO3- mucosal-to-serosal flux under 5% CO2 was 40% larger than the opposing flux, giving a net flux in the mucosal-to-serosal direction. This net flux was inhibited by acetazolamide. In CO2-free conditions, there was no detectable net flux; however, acetazolamide and PGF(2alpha) attenuated the mucosal-to-serosal flux and established an apparent secretion of HCO3-. A model is presented that depicts twelve vectors or components to the CO2 plus HCO3- fluxes in the frog skin. This model can accurately reproduce the experimental values measured from unidirectional fluxes of CO2 and HCO3- under a variety of conditions and can explain the effects of PGF(2alpha) on unidirectional 14C-labeled fluxes as a consequence of inhibition of H+ secretion to the apical bath, similar to what was previously suggested by our laboratory using a different methodological approach. The present method, utilizing radiolabeled HCO3-, may be useful as a means to evaluate the mechanism of action of hormones and drugs that may regulate acid-base homeostasis by altering proton and bicarbonate transport processes.

Animals↗
PubMed1977

Insulin-mediated Na+ transport in the toad urinary bladder.

The characteristics of insulin-induced Na+ transport in the toad urinary bladder were determined and compared to those of aldosterone. Bladders were mounted in modified Ussing chambers, and standard short-circuit current techniques were employed to measure transepithelial Na+ transport. Insulin added to the serosal medium is much more effective than insulin added to the mucosal medium. Serosal insulin concentrations from 10(1) to 10(3) muU/ml increase both the initial rate and the final level of Na+ transport achieved, whereas concentrations from 10(3) to 10(5) muU/ml increase only the initial rate of Na+ transport. Insulin-induced Na+ transport probably does not require glucose. Both insulin- and aldosterone-induced Na+ transport are directly proportional to serosal (but not mucosal) K+ concentration over the physiologic range (2.0-7.0 meq/liter). However, cycloheximide abolishes aldosterone- but not insulin-induced Na+ transport. In addition, insulin stimulates Na+ transport after a maximal response to aldosterone, and aldosterone stimulates Na+ transport after a maximal response to insulin. Thus, although they have several similar characteristics, insulin and aldosterone have at least partially independent mechanisms of action on Na+ transport in the toad urinary bladder.

Aldosterone↗
PubMed1979

Amphotericin B and K+ transport across excised toad urinary bladder.

The transmural electric PD of bladders bathed by Na2SO4 Ringer was not affected by amphotericin (5 x 10(-6) M, mucosal) but the PD followed the direction for K+ diffusion in the presence of a transmural K+ gradient. Increases in bathing solution K+ increased conductance. Ouabain pretreatment did not affect drug-induced changes in PD or conductance. Unidirectional fluxes of radiolabeled Na+ and K+ but not SO42- across the short-circuited bladder were increased by amphotericin. Ninety percent of the rise in the serosal-to-mucosal flow of Na+ disappeared when mucosal Na+ was replaced by choline. Amphotericin induced a 20-fold increase in mucosal-to-serosal K+ flux but K+ serosal-to-mucosal flow increased 200-fold. This flux asymmetry persisted for 110 min, was abolished by pre- or posttreatment with ouabain, and was immeasurable when bathing solution K+ was increased from 2.4 to 59 meq/liter. With 2.4 meq K+/liter the ratio of active Na+ reabsorption to K+ secretion was 8 to 1, but K+ secretion was not closely linked to Na+ transport. The results suggest that amphotericin induces a paracellular K+-selective path, Na+ isotope exchange, and K+ secretion.

Amphotericin B↗
PubMed1980

Inhibition of short-circuit current in toad urinary bladder by inhibitors of glandular kallikrein.

Aprotinin, a reversible inhibitor, and D-Phe-Phe-Arg-chloromethyl ketone (DPPA), an irreversible inhibitor of mammalian glandular kallikreins, decreased short-circuit current (SCC) in the isolated toad urinary bladder. Both were more potent and rapidly acting on the mucosal than serosal surface. The maximal inhibition in basal SCC was 29% for aprotinin and 41% for DPPA at concentrations of 7.0 X 10(-6) and 1.0 X 10(-5) M, respectively. SCC inhibition with mucosal aprotinin was reversed by rinsing, whereas inhibition with mucosal DPPA was not reversible. The presence of either agent in the mucosal bath inhibited the SCC increase to serosal vasopressin, but neither modified this response when present in the serosal bath. Neither agent affected basal or vasopressin-stimulated osmotic water permeability. Aprotinin did not prevent aldosterone-induced increases in SCC. Soybean trypsin inhibitor, an inhibitor of plasma but not glandular kallikrein, did not affect SCC. We postulate that these inhibitors of mammalian glandular kallikreins act upon some accessible serine proteinase(s) to reduce short-circuit current. This protein(s) might be an amphibian homologue of mammalian renal kallikrein.

Aldosterone↗
PubMed1986

Fluctuations in intracellular pH associated with vasopressin stimulation.

Intracellular pH (pHi) was estimated in paired hemibladders isolated from Dominican toads (Bufo marinus) by the tissue distribution of [14C]5,5'-dimethyl-2,4-oxazolidinedione and [3H]inulin. Tissues were incubated with isotopes for 30 min to correlate changes in pHi with the approximate time of peak vasopressin (VP)-induced water flow. At serosal pH 7.1 in the presence of an osmotic gradient, the intracellular hydrogen ion concentration [( H+]i) after 30 min of VP (20 mU/ml) stimulation was 8.29 +/- 0.23 X 10(-8) M (pHi 7.08) compared with 5.19 +/- 0.46 X 10(-8) M (pHi 7.28) in unstimulated paired controls (n = 5, P less than 0.001). The cyclic AMP (cAMP) analogue 8-(p-chlorophenylthio)-cAMP (10(-5) M) mimicked the VP effects. A similar change was observed at serosal bath pH 8.2, where [H+]i was 1.67 +/- 0.06 X 10(-8) M (pHi 7.78) with VP vs. 1.11 +/- 0.04 X 10(-8) M (pHi 7.95) in matched controls (n = 8, P less than 0.001). In all cases, the hydroosmotic response was associated with a significant decrease in inulin space. When the osmotic gradient was eliminated with Ringer solution or isotonic sorbitol in the mucosal bath, VP produced a smaller decrease in pHi (approximately 0.08 pH units) at both serosal pH. 31P-nuclear magnetic resonance spectra showed a similar downward trend in pHi with cell swelling. When vasopressin was removed from the bath, pHi and inulin space in stimulated hemibladders returned to pretreatment values within 30 min, and the tissues were again capable of a maximum hydroosmotic response if rechallenged with the hormone.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

NBD-taurine uptake by alpha-type carbonic anhydrase cells of turtle bladder.

The uptake of the fluorescent anion, N-(7-nitrobenz-2-oxa-1,3 diazol-4-yl)aminoethanosulfonic acid-taurine (NBD-T) was examined in sheets of turtle bladder epithelial cells after either serosal or mucosal exposure to the fluorescent anion. Serosal uptake of NBD-T into a population of epithelial cells was demonstrated in thin epithelial sheets scraped from bladder sacs exposed to low (0.5 mM) concentrations of NBD-T sufficient to cause fluorescence in turtle erythrocytes. In nine sheets NBD-T fluorescence was observed in 14.4 +/- 1.3% of epithelial cells; by phase-contrast microscopy of the same fields, these cells were nongranular or carbonic anhydrase (CA) cells. An additional 8.1 +/- 1.0% of cells was nongranular, but failed to exhibit fluorescence after serosal NBD-T exposure, consistent with a beta-CA cell population. Apical uptake of NBD-T into epithelial cells was demonstrable only at high (5 mM) mucosal concentrations in both thin sheets and superfused bladder segments. In thin sheets, NBD-T fluorescence was observed in 15.8 +/- 0.7% of cells and appeared to have a punctate subapical distribution; phase-contrast of the same fields (n = 46) revealed a nongranular cell population of 21.9 +/- 0.9%. Nongranular cells corresponded closely to CA cells as identified with carboxyfluorescein fluorescence. Hence, apical NBD-T was taken up primarily by alpha-CA cells. In conclusion, NBD-T is transported by alpha-CA cells either across the basolateral membrane with high affinity comparable to that of turtle red cell band 3 protein or across the apical membrane with low affinity via a less-specific mechanism such as endocytosis.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Cell swelling increases intracellular free [Ca] in cultured toad bladder cells.

We examined the effect of cell swelling on intracellular free calcium concentration ([Ca]i) in cultured toad bladder cells (TB-M) grown as a polarized monolayer on collagen-coated filters. [Ca]i was measured by use of fura-2, fluorescence microscopy, and simple video imaging. In preliminary experiments we determined that reducing ionic strength by 15% had no effect on the Kd of fura-2, indicating that the dye could be used to examine the effects of cell swelling on [Ca]i. Reducing the osmolality of the serosal bathing medium by 15% caused [Ca]i to increase within 10 s from 97 +/- 9 to 354 +/- 88 nM (n = 5). By 2 min [Ca]i had declined to 163 +/- 22 nM. The increase in [Ca]i was not caused by a fall in Na concentration ([Na]) because isosmotic reduction of serosal [Na] did not result in an increase in [Ca]i. The swelling-induced increase in [Ca]i could be abolished by lowering serosal [Ca] to 200 nM and by addition of lanthanum. The calcium-channel blockers nitrendipine and verapamil also inhibited the swelling-induced increase in [Ca]i, although to different degrees. These experiments demonstrate that swelling of cultured toad bladder cells results in a significant increase in [Ca]i by enhancing the rate of calcium entry across the basolateral membrane, possibly through a calcium channel.

Animals↗
PubMed1991

Low-dose glucocorticoids maintain Na-H exchange in distal colon of adrenalectomized rats.

With in vivo perfusion we demonstrated that physiological doses of glucocorticoids restore Na and Cl absorption in adrenalectomized rat colon. The absorption is spironolactone and amiloride resistant and is inhibited by the Na-H inhibitor, 5-(N-ethyl-N-isopropyl)amiloride (EIPA), suggesting that glucocorticoids modulate Na-H antiport. The present in vitro study examines pathways mediated by glucocorticoids in adrenalectomized rat distal colon and rectum. In vivo administration of 2.5 micrograms/100 g body wt dexamethasone did not alter serosal-to-mucosal flux or tissue electrical parameters but restored mucosal-to-serosal flux and net Na and Cl absorption within 2-3 h of administration to levels found in intact rat colon. Transport was not inhibited by 10(-5) M amiloride but was eliminated by 10(-5) M EIPA. After 26 h of dexamethasone, an amiloride-resistant short-circuit current was stimulated, accompanied by increased residual ion flux in rectum, but not distal colon, suggesting that a delayed or secondary effect of glucocorticoids is stimulation of electrogenic anion secretion. Thus adrenalectomy reduces net ion flux in distal colon by its effect on electroneutral mucosal-to-serosal NaCl flux. Small doses of glucocorticoids completely ameliorate this effect via stimulation of the Na-H antiport. Glucocorticoids maintain basal electroneutral NaCl absorption in distal rat colon.

Adrenalectomy↗
PubMed1984

Asymmetry of canine tracheal epithelium: osmotically induced changes.

The symmetry of osmotic conductivity of the canine tracheal epithelial cells was examined in vitro. When an osmotic load of 100 mosM sucrose was added to the serosal bathing solution, no change in the transepithelial potential difference was observed in 15 tissue preparations. In contrast, when the same osmotic load was added to the mucosal bathing solution, there was a rapid decrease in the transepithelial potential difference of 3.9 +/- 0.5 mV (n = 23); ouabain (10(-4) M) eliminated this change. Tissues that had been exposed to the osmotic load added to either the mucosal or serosal side were compared with the control using light and electron microscopy. When the osmotic load was added to the mucosal fluid, there was no change in the nuclear-to-cytoplasmic area ratio of the cell types examined. However, when the same osmotic load was added to the serosal fluid, a marked increase in the nuclear-to-cytoplasmic area ratio of the ciliated cells was observed. This finding indicated cell shrinkage. Dilution potentials measured by substituting NaCl with mannitol also showed asymmetry. The morphological features are probably caused by differences in the osmotic conductivity (Lp) of the basolateral and apical cell membranes, with the Lp of the apical membrane being less than that of the basolateral membrane. The basis for osmotically induced potentials remained undetermined.

Animals↗
PubMed1985

Electrical properties of monolayers cultured from cells of human tracheal mucosa.

Dispersed isolated cells were obtained from human tracheal mucosa by digestion with collagenase. Up to 1.5 X 10(8) cells were obtained per trachea and showed up to 95% viability, as judged by trypan blue exclusion. When grown in culture, the cells formed monolayers after approximately 4 days. Electron microscopy of the monolayers revealed a polarized structure. An apical membrane, containing microvilli and a pronounced glycocalyx, was separated from a relatively unspecialized basolateral membrane by typical tight junctions. Monolayers grown on nucleopore filters showed resistances of 44-1,800 omega. cm2 and transepithelial potential differences of 0.1-7.6 mV. Short-circuit current (Isc) was increased by isoproterenol, prostaglandins E2 and F2 alpha, and bradykinin. The loop diuretic, bumetanide, reduced Isc when added to the basolateral (serosal) side but had no effect from the apical (mucosal) side of the monolayers. Furosemide and MK-196 also inhibited Isc. Mucosal amiloride inhibited Isc. Serosal amiloride or mucosal ouabain had no effect on Isc. Serosal ouabain brought Isc to zero after approximately 15 min.

Amiloride↗
PubMed1986

Ion transport across cat and ferret tracheal epithelia.

Sheets of trachea from ferret and cat were mounted in Ussing chambers and continuously short circuited. Under resting conditions, in both the cat and ferret there was little or no Cl secretion, and Na absorption accounted for most of the short-circuit current (Isc). Ouabain (10(-4) M, serosal bath) reduced Isc to zero in 30-60 min. This decline was matched by a decrease in net Na absorption. Amiloride (10(-4) M, luminal bath) caused a significant decrease in Isc and conductance (G) in both species. Bumetanide (10(-4) M, serosal bath) had negligible effects on Isc and G. In both species, isoproterenol increased Isc by stimulating Cl secretion. Methacholine induced equal amounts of Na and Cl secretion, with little change in Isc. In the cat, prostaglandins E2 and F2 alpha and bradykinin increased Isc, responses which were abolished in Cl-free medium. In open-circuited cat tissues, Na flux from the serosal to mucosal side was measured simultaneously with the secretion of nondialyzable 35S. Prostaglandins E1, E2, and F2 alpha, histamine, bradykinin, methacholine and isoproterenol all increased both Na and 35S-mucin secretion.

Amiloride↗
PubMed1988

Osmotic stimuli induce epithelial-dependent relaxation in the guinea pig trachea.

Epithelium in airways, like endothelium in blood vessels, may regulate responses of adjacent smooth muscle. To study the intact trachea from guinea pigs we developed an in vitro preparation that permits independent stimulation from either the inner epithelial surface or the outer serosal surface. The whole guinea pig trachea was excised, cannulated, and perfused at a constant flow with Krebs-Henseleit (KH) solution that was in direct contact with the inner epithelial-lined surface. The outer serosal surface of the trachea was immersed in a separate system (bath) containing KH solution. Tracheal responses were assessed by measuring the pressure drop between the tracheal inlet and the outlet under conditions of constant flow. When the trachea was precontracted with carbachol or KCl, hyperosmolar stimuli (KCl, mannitol, urea, or NaCl) produced concentration-dependent relaxation when applied to the inner epithelial surface. Relaxation was not produced when the hyperosmolar stimulus was applied to the serosal surface and was markedly reduced or abolished when the epithelial surface had been physically damaged or removed. These results indicate that hyperosmotic stimuli induce epithelial-dependent relaxation of trachea. A defect in this mechanism may be partially responsible for the bronchoconstriction seen in asthmatic subjects after exercise.

Airway Resistance↗
PubMed1989

Protective role of epithelium in the guinea pig airway.

We developed an in vitro system to assess the role of the epithelium in regulating airway tone using the intact guinea pig trachea (J. Appl. Physiol. 64: 466-471, 1988). This method allows us to study the response of the airway when its inner epithelial surface or its outer serosal surface is stimulated independently. Using this system we evaluated how the presence of intact epithelium can affect pharmacological responsiveness. We first examined responses of tracheae with intact epithelium to histamine, acetylcholine, and hypertonic KCl when stimulated from the epithelial or serosal side. We then examined the effect of epithelial denudation on the responses to these agonists. With an intact epithelium, stimulation of the inner epithelial side always caused significantly smaller changes in diameter than stimulation of the outer serosal side. After mechanical denudation of the epithelium, these differences were almost completely abolished. In the absence of intact epithelium, the trachea was 35-fold more sensitive to histamine and 115-fold more sensitive to acetylcholine when these agents were applied to the inner epithelial side. In addition, the presence of an intact epithelium almost completely inhibited any response to epithelial side challenge with hypertonic KCl. These results indicate that the airway epithelial layer has a potent protective role in airway responses to luminal side stimuli, leading us to speculate that changes in airway reactivity measured in various conditions including asthma may result in part from changes in epithelial function.

Acetylcholine↗
PubMed1989

Transepithelial prostacyclin gradient in isolated canine trachea.

Cyclooxygenase products of arachidonic acid, potential modulators of airway smooth muscle, have recently been described in bronchoalveolar lavage from canine lungs. To evaluate the possibility that airway epithelium represents a barrier to movement of prostacyclin (PGI2), an important bronchodilator synthesized by isolated airway, we measured the concentrations of 6-oxoprostaglandin F1 alpha (6-oxo-PGF1 alpha), the stable degradation product of PGI2, on the mucosal and serosal sides of isolated canine tracheal segments (CTS) mounted in Ussing chambers. 6-oxo-PGF1 alpha was measured by radioimmunoassay after purification by high-performance liquid chromatography. The concentration of 6-oxo-PGF1 alpha was significantly higher on the serosal than the mucosal side of CTS (1,262 +/- 252 vs. 390 +/- 168 pg.min-1.g-1, n = 8, P less than 0.05). A significant correlation was present between 6-oxo-PGF1 alpha measured on both sides of each CTS (r = 0.778, n = 26, P less than 0.01). 6-oxo-PGF1 alpha production from CTS stripped of mucosa was significantly greater than from isolated mucosa. Radiochromatograms obtained after incubation with [3H]arachidonic acid and calcium ionophore A23187 confirmed PGI2 as the predominant cyclooxygenase product of the submucosa, whereas the mucosa produced only small amounts of PGI2 in proportion to other cyclooxygenase products. PGI2 (10(-8) to 10(-6) M) applied to the mucosal surface of closed tracheal segments precontracted with histamine resulted in no significant relaxation, whereas serosal application showed a concentration-dependent effect. Radiolabeled 6-oxo-PGF1 alpha did not cross the isolated epithelium.(ABSTRACT TRUNCATED AT 250 WORDS)

6-Ketoprostaglandin F1 alpha↗
PubMedDate not supplied

Sodium chloride transport of normal and dietary enlarged rat cecum in vitro.

Sodium chloride transport across isolated cecum mucosa was investigated in normal rats and rats with adaptive cecum growth induced by dietary polyethylene glycol (PEG). The normal cecum absorbed Cl in excess of Na with a small short-circuit current (ISC). Dietary adaptation led to large equivalent increments of Na and Cl net absorption without adequate ISC change. Inhibitor studies (mucosal amiloride 10(-3) and 10(-4) M; mucosal 4, 4-diisothiocyanatostilbene-2,2-disulfonic acid 5 x 10(-5) M; serosal furosemide 10(-3) M; serosal ouabain 10(-3) M) suggested that normal cecal NaCl absorption involves electroneutral Na/H and Cl/HCO3 exchange at the apical and Na-K-ATPase-mediated exit across the basolateral cell membrane. Dietary adaptation stimulates the loosely coupled antiports and possibly activates a small serosally located NaCl cotransport. Comparative histology showed flattening of all tissue layers and widening of crypts in PEG animals. Crypt widening may facilitate ion access to underutilized transport sites and, at least in part, explain the increased absorption of the enlarged cecum.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗
PubMedDate not supplied

Stimulatory effect of nitric oxide on bicarbonate secretion in bullfrog duodenums in vitro.

The effect of nitric oxide (NO) on HCO-3 secretion was examined in vitro using an isolated preparation of bullfrog duodenum. The tissue was bathed in unbuffered Ringer's solution gassed with 100% O2 on the mucosal side and HCO-3 Ringer's solution gassed with 95% O2-5% CO2 on the serosal side. The HCO-3 secretion was measured by the pH-stat method using 2 mmol/l HCl as the titrant to keep the mucosal pH at 7.4. (+/-)-(E)-Ethyl-2-[(E)-hydroxyimino]-5-nitro-3-hexenamine (NOR3) was used as a NO donor and added to the serosal solution. To analyze the NOR3 action on HCO-3 secretion, the effects of dibutyryl adenosine-3',5'-cyclic monophosphate (dbcAMP), dibutyryl guanosine-3',5'-cyclic monophosphate (dbcGMP), methylene blue, and indomethacin on the HCO-3 response were also examined. NOR3 (1x10(-4) and 3x10(-4) mol/l) caused an increase in HCO-3 secretion in a dose-dependent manner, and this effect appeared with an about 30-min time lag, reaching the level of 1.5-2.5 times greater than basal values at 1-2 h later. Both dbcAMP (1x10(-3) mol/l) and dbcGMP (1x10(-3) mol/l) also caused a significant increase in HCO-3 secretion in bullfrog duodenums in vitro, although the onset of the HCO-3 response to dbcGMP was delayed as compared to the former. The stimulatory action of NOR3 on duodenal HCO-3 secretion was significantly attenuated by methylene blue (5x10(-5) mol/l) and indomethacin (1x10(-5) mol/l), the latter also inhibiting the HCO-3 response to dbcGMP. The release of prostaglandin E2 in the serosal solution was significantly increased after addition of NOR3 (3x10(-4) mol/l) and dbcGMP (1x10(-3) mol/l) in an indomethacin-sensitive manner. These results suggest that the NO donor increases duodenal HCO-3 secretion in vitro, and this action of NO donor is cGMP-dependent and mediated by endogenous prostaglandins. Duodenal HCO-3 secretion may be regulated locally by NO/cGMP in addition to prostaglandin/cAMP.

Animals↗