Membrane Resistances and Electromotive Forces during Stimulation of Chloride Secretion in the Canine Tracheal Epithelium

CHEST Journal ◽  
1982 ◽  
Vol 81 (5) ◽  
pp. 3-4
Author(s):  
Michael J. Welsh ◽  
Philip L. Smith ◽  
Raymond A. Frizzell
Keyword(s):  
Chloride Secretion ◽  
Tracheal Epithelium ◽  
Stimulation Of

Changes in intracellular sodium with chloride secretion in dog tracheal epithelium

1986 ◽  
Vol 250 (4) ◽  
pp. C646-C650 ◽  
Author(s):  
S. R. Shorofsky ◽  
M. Field ◽  
H. A. Fozzard
Keyword(s):  
Steady State ◽  
Kinetic Models ◽  
Short Circuit ◽  
Short Circuit Current ◽  
Chloride Secretion ◽  
Tracheal Epithelium ◽  
Cl Secretion ◽  
Intracellular Na Activity ◽  
Sufficient Energy ◽  
Stimulation Of

Na-selective microelectrodes were employed to investigate the mechanism of Cl secretion by canine tracheal epithelium. In control tissues with a mean short-circuit current (Isc) of 30.1 microA/cm2, the intracellular Na activity (aiNa) was 10.7 mM. Following steady-state stimulation of Cl secretion with epinephrine (Isc = 126.4 microA/cm2), aiNa was 21.3 mM. These data indicate that there is sufficient energy in the Na gradient to drive Cl secretion by this tissue. When analyzed with simple kinetic models for the Na-K pump, they also suggest that the basolateral entry step involves the Na-K-2Cl cotransporter.

Endothelin stimulates chloride secretion across canine tracheal epithelium

1991 ◽  
Vol 261 (2) ◽  
pp. L188-L194 ◽  
Author(s):  
P. I. Plews ◽  
Z. A. Abdel-Malek ◽  
C. A. Doupnik ◽  
G. D. Leikauf
Keyword(s):  
Epithelial Cells ◽  
Short Circuit ◽  
Second Messengers ◽  
Short Circuit Current ◽  
Chloride Secretion ◽  
Tracheal Epithelium ◽  
Membrane Phospholipids ◽  
Cl Secretion ◽  
Tracheal Epithelial Cells ◽  
Tracheal Epithelial

The endothelins (ET) are a group of isopeptides produced by a number of cells, including canine tracheal epithelial cells. Because these compounds are endogenous peptides that may activate eicosanoid metabolism, we investigated the effects of ET on Cl secretion in canine tracheal epithelium. Endothelin 1 (ET-1) was found to produce a dose-dependent change in short-circuit current (Isc) that increased slowly and reached a maximal value within 10-15 min. When isopeptides of ET were compared, 300 nM ET-1 and ET-2 produced comparable maximal increases in Isc, whereas ET-3 produced smaller changes in Isc (half-maximal concentrations of 2.2, 7.2, and 10.4 nM, respectively). Ionic substitution of Cl with nontransported anions, iodide and gluconate, reduced ET-1-induced changes in Isc. Furthermore, the response was inhibited by the NaCl cotransport inhibitor, furosemide. In paired tissues, ET-1 significantly increased mucosal net 36Cl flux without significant effect on 22Na flux. The increase in Isc induced by ET was diminished by pretreatment with indomethacin. The second messengers mediating the increase in Isc were investigated in cultured canine tracheal epithelial cells. ET-1 stimulated the release of [3H]arachidonate from membrane phospholipids, increased intracellular Ca2+ (occasionally producing oscillations), and increased adenosine 3',5'-cyclic monophosphate accumulation. The latter was diminished by indomethacin. Thus ET is a potent agonist of Cl secretion (with the isopeptides having the following potency: ET-1 greater than or equal to ET-2 greater than ET-3) and acts, in part, through a cyclooxygenase-dependent mechanism.

Role of CFTR in chloride secretion across human tracheal epithelium

1995 ◽  
Vol 269 (5) ◽  
pp. L561-L566 ◽  
Author(s):  
B. Q. Shen ◽  
R. J. Mrsny ◽  
W. E. Finkbeiner ◽  
J. H. Widdicombe
Keyword(s):  
Apical Membrane ◽  
Short Circuit ◽  
Primary Cultures ◽  
Short Circuit Current ◽  
Chloride Secretion ◽  
Culture Conditions ◽  
Tracheal Epithelium ◽  
Disulfonic Acid ◽  
Acetoxymethyl Ester ◽  
Cl Channels

We have tested two hypotheses: 1) the cystic fibrosis transmembrane conductance regulator (CFTR) represents the predominant Cl conductance in the apical membrane of human tracheal epithelium, and 2) CFTR in this tissue is close to maximally activated under baseline conditions. In support of the first hypothesis, we found 1) when the level of differentiation of cultures was varied by varying the culture conditions, there was a significant positive correlation between the levels of CFTR and the magnitude of mediator-induced Cl secretion. 2) Amiloride-insensitive baseline short-circuit current (Isc) and mediator-induced increases in Isc were inhibited by diphenylamine-2-carboxylic acid (DPAC) but not by 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS), a pharmacology consistent with passage of apical membrane Cl current through CFTR; Ca-activated Cl channels are inhibited by DIDS but not by DPAC. 3) Raising temperature from 22 degrees to 37 degrees C increased 125I efflux, and this increase was inhibited by DPAC and blockers of protein kinase A, but not by DIDS or 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid-acetoxymethyl ester. In support of the second hypothesis, we have earlier shown [M. Yamaya, W.E. Finkbeiner, S.Y. Chun, and J.H. Widdicombe. Am. J. Physiol. 262 (Lung Cell. Mol. Physiol. 6): L713-L724, 1992] that adenosine 3',5'-cyclic monophosphate (cAMP)-elevating agents are essentially without effect on Isc across primary cultures of human tracheal epithelium. Here, we further show that these agents are also usually without effect on 125I efflux; the mean increase in efflux in response to elevating cAMP was approximately 20% that of raising temperature from 22 degrees to 37 degrees C.

Atriopeptin stimulation of rectal gland function in Squalus acanthias

1985 ◽  
Vol 249 (3) ◽  
pp. R348-R354 ◽  
Author(s):  
R. Solomon ◽  
M. Taylor ◽  
D. Dorsey ◽  
P. Silva ◽  
F. H. Epstein
Keyword(s):  
Volume Expansion ◽  
Epithelial Transport ◽  
Extracellular Volume ◽  
Chloride Secretion ◽  
Hormonal Control ◽  
Rectal Gland ◽  
Gland Function ◽  
Stimulation Of

The rectal gland of the shark plays a significant role in the homeostasis of extracellular volume. Regulation of rectal gland function is under hormonal control, but the precise identity of the humoral mediator is unknown. Atriopeptin stimulates rectal gland chloride secretion in vivo. This stimulation of epithelial transport is accompanied by systemic and local hemodynamic effects. Atriopeptin also stimulates chloride secretion by the in vitro perfused rectal gland, an effect that is not accompanied by hemodynamic changes. Extracts of shark heart, but not muscle, brain, kidney, or intestine, contain a heat-stable trypsin-sensitive substance capable of in vitro stimulation of rectal gland chloride secretion. Electron micrographic analysis reveals multiple neurosecretory-like granules in atrial cardiocytes that are only rarely seen in ventricular cardiocytes. By using the in vitro perfused gland as a biologic assay, serum obtained after extracellular volume expansion reveals the presence of a rectal gland stimulatory factor that is not present in serum before expansion. These results are consistent with the hypothesis that atriopeptin is present in shark cardiocytes and is released during volume expansion. The atriopeptin stimulates rectal gland chloride secretion, providing a negative feedback mechanism for the regulation of extracellular volume.

Na-K-Cl cotransport in nystatin-treated tracheal cells: regulation by isoproterenol, apical UTP, and [Cl]i

1994 ◽  
Vol 266 (5) ◽  
pp. C1440-C1452 ◽  
Author(s):  
M. Haas ◽  
D. G. McBrayer
Keyword(s):  
Epithelial Cells ◽  
Plasma Membranes ◽  
Basolateral Membrane ◽  
Primary Cultures ◽  
Chloride Secretion ◽  
Airway Epithelial Cells ◽  
Tracheal Epithelial Cells ◽  
Cl Transport ◽  
Monovalent Ions ◽  
Stimulation Of

Chloride secretion in mammalian airway epithelia is stimulated by beta-adrenergic agonists via an adenosine 3',5'-cyclic monophosphate (cAMP)-dependent mechanism and by apical triphosphate nucleotides (ATP, UTP) via a cAMP-independent mechanism. Both types of secretagogues are known to stimulate apical Cl channels in airway cells; however, to maintain a stimulated rate of secretion, basolateral Cl influx via Na-K-Cl cotransport must be upregulated in parallel with apical Cl efflux. To examine the regulation of basolateral cotransport activity and its relationship to apical Cl efflux, we examined Cl transport in confluent primary cultures of dog tracheal epithelial cells treated with nystatin, an antibiotic that increases the permeability of plasma membranes to small monovalent ions, including Cl. By applying nystatin to the apical membrane of these cultures, apical Cl permeability could be increased to the point where transepithelial Cl transport is limited by transport across the basolateral membrane, which reflects primarily the activity of the cotransporter. In cultures of tracheal cells not treated with nystatin, transepithelial (basolateral-to-apical) 36Cl flux was increased two- to threefold by exposure to isoproterenol (5 microM, basolateral) or apical UTP (10 microM). Apical application of nystatin (400 units/ml) increased the basal level of transepithelial 36Cl flux approximately 1.5-fold and eliminated UTP stimulation of this flux, although an approximately twofold stimulation by isoproterenol persisted. Nystatin treatment also abolished UTP stimulation of saturable, basolateral [3H]bumetanide binding, a measure of functioning Na-K-Cl cotransporters in these cells; isoproterenol stimulation of binding was only mildly inhibited by nystatin treatment. Lowering intracellular Cl concentration ([Cl]i) by incubating cultures with apical media containing nystatin and reduced [Cl] (NO3 replacement) increased both basolateral-to-apical 36Cl flux and [3H]bumetanide binding in the absence of secretagogues or cell shrinkage. The results support our previous suggestion, based entirely on [3H]bumetanide binding [M. Haas, D. G. McBrayer, and J. R. Yankaskas. Am. J. Physiol. 264 (Cell. Physiol. 32): C189-C200, 1993], that UTP stimulation of basolateral Na-K-Cl cotransport in airway epithelial cells is entirely secondary to, and requires, an increase in apical Cl efflux, and further suggest that a decrease in [Cl]i may be a signal for cotransport activation in response to UTP. In addition, a cAMP-dependent cascade initiated by isoproterenol appears to directly stimulate the cotransporter.

Adenosine 3',5'-cyclic monophosphate stimulates chloride secretion in A6 epithelia

1986 ◽  
Vol 251 (5) ◽  
pp. C810-C814 ◽  
Author(s):  
M. Yanase ◽  
J. S. Handler
Keyword(s):  
Short Circuit ◽  
Short Circuit Current ◽  
Chloride Secretion ◽  
Apical Surface ◽  
Cyclic Monophosphate ◽  
A6 Epithelia ◽  
In Series ◽  
Cl Channels ◽  
Solution Bathing ◽  
Stimulation Of

Basal and aldosterone-stimulated short-circuit current (Isc) of A6 epithelia are known to be equivalent to net apical to basal Na flux and are completely inhibited by 0.05 mM amiloride added to the solution bathing the apical surface of the epithelium. In the absence of amiloride, the Isc stimulated by adenosine 3',5'-cyclic monophosphate (cAMP) is also equivalent to net apical to basal Na flux. However, amiloride does not completely inhibit the cAMP-stimulated Isc. In this study, the cAMP-stimulated, amiloride-insensitive Isc was characterized, using vasopressin or forskolin to raise cell cAMP. After basal Isc is inhibited by amiloride, forskolin stimulates Isc, conductance, and bidirectional 36Cl flux. Stimulation of Isc depends on the presence of both Na and Cl; stimulation of conductance depends on the presence of Cl. 36Cl flux studies showed that the cAMP-stimulated, amiloride-insensitive Isc is equivalent to net Cl flux. It is inhibited by ouabain and by furosemide or bumetanide added to the solution bathing the basal surface of the epithelium. In view of the effect of cAMP in some other epithelia, we suggest that cAMP activates apical membrane Cl channels that are in series with a Na-K-Cl cotransporter in the basolateral plasma membrane.

Alteration of chloride secretion across canine tracheal epithelium by lipoxygenase products of arachidonic acid

1986 ◽  
Vol 250 (1) ◽  
pp. F47-F53 ◽  
Author(s):  
G. D. Leikauf ◽  
I. F. Ueki ◽  
J. H. Widdicombe ◽  
J. A. Nadel
Keyword(s):  
Arachidonic Acid ◽  
Short Circuit ◽  
Thromboxane A2 ◽  
Short Circuit Current ◽  
Chloride Secretion ◽  
Tracheal Epithelium ◽  
Release Rates ◽  
Thromboxane Synthetase ◽  
Lipoxygenase Products ◽  
Do So

We examined whether the leukotrienes (LT) B4, C4, D4, and E4, and 5-, 12-, and 15-hydroxyeicosatetraenoic (HETE) acids alter the electrical properties of canine tracheal epithelium. Short-circuit current (ISC) increased by 20.3 +/- 4.3 and 25.9 +/- 6.5 microA/cm2 after LTC4 and LTD4 addition, was unchanged following LTB4, LTE4, 5-, or 15-HETE addition, and was decreased by 10 +/- 3% after 12-HETE addition. LTC4- and LTD4-induced increases in ISC were dependent on the presence of Cl and were equal to the increases in net 36Cl flux toward the mucosa. The cyclooxygenase inhibitor indomethacin (10(-5) M) or the phospholipase inhibitor mepacrine (10(-5) M) diminished increases in ISC. The release rate of prostaglandins E2 and F2 alpha and thromboxane B2 rose from 8.2 +/- 2.3, 2.3 +/- 0.5, and 1.1 +/- 0.5 to 15.5 +/- 3.3, 6.0 +/- 1.4, and 4.0 +/- 0.8 ng . cm-2 . h-1, respectively, after LTC4 addition, and from 6.9 +/- 1.4, 2.5 +/- 1.1, and 1.7 +/- 1.3 to 20.2 +/- 3.1, 10.5 +/- 3.1, and 5.2 +/- 2.4 ng . cm-2 . h-1, respectively, after LTD4 addition. The release rates of 6-keto-prostaglandin F1 alpha were unchanged. A thromboxane A2 mimetic, U46619, failed to increase ISC and thromboxane synthetase inhibitors OKY-046 and dazmegrel failed to inhibit the induced increases in ISC, suggesting that thromboxane has little effect on ISC. Thus lipoxygenase products of arachidonic acid can modulate Cl secretion by the canine tracheal epithelium and do so through the release of cyclooxygenase products, including prostaglandins E2 and F2 alpha.

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