scholarly journals Interferon-γ Down-regulates Adenosine 2b Receptor-mediated Signaling and Short Circuit Current in the Intestinal Epithelia by Inhibiting the Expression of Adenylate Cyclase

2004 ◽  
Vol 280 (6) ◽  
pp. 4048-4057 ◽  
Author(s):  
Vasantha Kolachala ◽  
Vivian Asamoah ◽  
Lixin Wang ◽  
Shanthi Srinivasan ◽  
Didier Merlin ◽  
...  
Keyword(s):  
Adenylate Cyclase ◽  
Short Circuit ◽  
Short Circuit Current ◽  
Interferon Γ ◽  
Intestinal Epithelia

Role of alpha 1- and alpha 2-adrenergic receptors in Cl- transport across frog corneal epithelium

1988 ◽  
Vol 255 (6) ◽  
pp. C724-C730 ◽  
Author(s):  
T. C. Chu ◽  
O. A. Candia
Keyword(s):  
Adenylate Cyclase ◽  
Corneal Epithelium ◽  
Apical Membrane ◽  
Short Circuit ◽  
Short Circuit Current ◽  
Negative Influence ◽  
Adenylate Cyclase System ◽  
Positive Effects ◽  
Cl Transport ◽  
Beta Agonists

Norepinephrine, 10(-6) M, reduced Cl- transport by 26% in 75% of isolated frog corneal epithelia. This inhibition was not previously reported. Since beta-adrenergic agonists are known to only stimulate Cl- transport, the action of specific alpha 1- and alpha 2-agonists on Cl- transport and electrical parameters was investigated. Phenylephrine, an alpha 1-agonist always stimulated the Cl(-)-dependent short-circuit current (Isc), but less than the beta-agonists. UK-14,304-18 (UK), a selective alpha 2-agonist, reduced both the Isc (by 31% at 10(-5) M) and the stroma-to-tear unidirectional Cl- flux. UK hyperpolarized the apical membrane potential difference and increased the transepithelial resistance and apical-to-basolateral resistance ratio. UK reduced forskolin-stimulated adenylate cyclase activity by 36%. The electrophysiological effects of UK are consistent with a reduction of the Cl- permeability at the apical membrane. Pretreatment with UK sensitized the tissue for a greater effect by forskolin. Results show that the frog corneal epithelium also possesses alpha 1- and alpha 2-receptors, the latter negatively coupled to the adenylate cyclase system. Cl- transport is thus regulated by an interaction between the positive effects of beta- and alpha 1-stimulation and the negative influence of alpha 2-stimulation.

scholarly journals Nobiletin Stimulates Chloride Secretion in Human Bronchial Epithelia via a cAMP/PKA-Dependent Pathway

2015 ◽  
Vol 37 (1) ◽  
pp. 306-320 ◽  
Author(s):  
Yuan Hao ◽  
Cindy S.T. Cheung ◽  
Wallace C.Y. Yip ◽  
Wing-hung Ko
Keyword(s):  
Cystic Fibrosis ◽  
Adenylate Cyclase ◽  
Cell Line ◽  
Short Circuit ◽  
Short Circuit Current ◽  
Chloride Secretion ◽  
Epithelial Cell Line ◽  
Electrical Measurements ◽  
Cl Secretion ◽  
Bronchial Epithelia

Background/Aims: Nobiletin, a citrus flavonoid isolated from tangerines, alters ion transport functions in intestinal epithelia, and has antagonistic effects on eosinophilic airway inflammation of asthmatic rats. The present study examined the effects of nobiletin on basal short-circuit current (ISC) in a human bronchial epithelial cell line (16HBE14o-), and characterized the signal transduction pathways that allowed nobiletin to regulate electrolyte transport. Methods: The ISC measurement technique was used for transepithelial electrical measurements. Intracellular calcium ([Ca2+]i) and cAMP were also quantified. Results: Nobiletin stimulated a concentration-dependent increase in ISC, which was due to Cl- secretion. The increase in ISC was inhibited by a cystic fibrosis transmembrane conductance regulator inhibitor (CFTRinh-172), but not by 4,4'-diisothiocyano-stilbene-2,2'-disulphonic acid (DIDS), Chromanol 293B, clotrimazole, or TRAM-34. Nobiletin-stimulated ISC was also sensitive to a protein kinase A (PKA) inhibitor, H89, and an adenylate cyclase inhibitor, MDL-12330A. Nobiletin could not stimulate any increase in ISC in a cystic fibrosis (CF) cell line, CFBE41o-, which lacked a functional CFTR. Nobiletin stimulated a real-time increase in cAMP, but not [Ca2+]i. Conclusion: Nobiletin stimulated transepithelial Cl- secretion across human bronchial epithelia. The mechanisms involved activation of adenylate cyclase- and cAMP/PKA-dependent pathways, leading to activation of apical CFTR Cl- channels.

A model eliciting transient responses

1984 ◽  
Vol 246 (1) ◽  
pp. R114-R121 ◽  
Author(s):  
E. B. Ekblad ◽  
V. Licko
Keyword(s):  
Gastric Mucosa ◽  
Adenylate Cyclase ◽  
Chemical Transformation ◽  
Transient Response ◽  
Short Circuit ◽  
Short Circuit Current ◽  
Transient Responses ◽  
Histamine Secretion ◽  
Cyclic Monophosphate ◽  
Camp Stimulation

A simple parametrically controlled chemical transformation scheme is used to exemplify a model with transient response to sustained stimulation. More complicated schemes are also discussed. Analyses of three experimental examples are given: short-circuit current changes in toad bladder exposed to adenosine 3',5'-cyclic monophosphate (cAMP) stimulation; histamine secretion in acetylcholine-stimulated frog gastric mucosa; and cAMP dynamics, expressed in terms of adenylate cyclase dynamics, in histamine-stimulated frog gastric mucosa. The model responds primarily to the changes of the stimulator level, although it is not a model with derivative control.

scholarly journals Molecular mechanisms for intestinal HCO3- secretion and its regulation by guanylin in seawater-acclimated eels

2019 ◽  
Author(s):  
Yoshio Takei ◽  
Marty K.S. Wong ◽  
Masaaki Ando
Keyword(s):  
Hormonal Regulation ◽  
Time Course ◽  
Molecular Mechanisms ◽  
Apical Membrane ◽  
Short Circuit ◽  
Basolateral Membrane ◽  
Short Circuit Current ◽  
Disulfonic Acid ◽  
Intestinal Epithelia ◽  
Mucosal Side

AbstractThe intestine of marine teleosts secretes HCO3- into the lumen and precipitates Ca2+ and Mg2+ in the imbibed seawater as carbonates to decrease luminal fluid osmolality and facilitate water absorption. However, reports on studies on the hormonal regulation of HCO3- secretion are just emerging. Here, we showed that guanylin (GN) applied to the mucosal side of intestinal epithelia increased HCO3- secretion in seawater-acclimated eels. The effect of GN on HCO3- secretion was slower than that on the short-circuit current, and the time-course of the GN effect was similar to that of bumetanide. Mucosal bumetanide and serosal 4,4’-dinitrostilbene-2,2’-disulfonic acid (DNDS) inhibited the GN effect, suggesting an involvement of apical Na+-K+-2Cl- cotransporter (NKCC2) and basolateral Cl-/HCO3- exchanger (AE)/Na+-HCO3- cotransporter (NBC) in the GN effect. However, mucosal DNDS and diphenylamine-2-carboxylic acid (DPC) failed to inhibit the GN effect, showing that apical AE and Cl- channel are not involved. To identify molecular species of possible transporters involved in the GN effect, we performed RNA-seq analyses followed by quantitative real-time PCR after transfer of eels to seawater. Among the genes upregulated after seawater transfer, those of Slc26a3a, b (DRAa, b) and Slc26a6a, c (Pat-1a, c) on the apical membrane of the intestinal epithelial cells, and those of Sls4a4a (NBCe1a), Slc4a7 (NBCn1), Slc4a10a (NBCn2a) and Slc26a1 (Sat-1) on the basolateral membrane were candidate transporters involved in HCO3- secretion. Judging from the slow effect of GN, we suggest that GN inhibits NKCC2b on the apical membrane and decreases cytosolic Cl- and Na+, which then activates apical DNDS-insensitive DRAa, b and basolateral DNDS-sensitive NBCela, n1, n2a to enhance transcellular HCO3- flux across the intestinal epithelia of seawater-acclimated eels.

scholarly journals A primary culture of guinea pig gallbladder epithelial cells that is responsive to secretagogues

2000 ◽  
Vol 279 (5) ◽  
pp. G866-G874 ◽  
Author(s):  
Pamela J. Gunter-Smith ◽  
Oluwakemi Abdulkadir ◽  
Latanya Hammonds-Odie ◽  
Mary Scanlon ◽  
Raquel Terrell
Keyword(s):  
Cell Culture ◽  
Epithelial Cells ◽  
Guinea Pig ◽  
Ion Transport ◽  
Short Circuit ◽  
Short Circuit Current ◽  
Intestinal Epithelia ◽  
Intracellular Ca ◽  
A Cell ◽  
Transport Inhibitors

We have developed a cell culture of guinea pig gallbladder epithelial cells with which to study ion transport. When grown on permeable supports, the cultured epithelia developed a transepithelial resistance ( R t) of ∼500 Ω · cm2. The epithelial cell origin of the cell culture was further confirmed by immunocytochemical localization of cytokeratin. Ionomycin and forskolin increased transepithelial voltage and short-circuit current ( I sc) and decreased R t. The response to ionomycin was transient, whereas that to forskolin was sustained. Both were attenuated by replacement of Cl− and/or HCO3 −. Mucosal addition of the anion transport inhibitors DIDS or diphenylamine-2-carboxylic acid (DPC) blocked the response to ionomycin. The response to forskolin was blocked by DPC but not by DIDS. Ionomycin, but not forskolin, increased intracellular Ca2+ concentration in fura 2-loaded cells. PGE2, histamine, vasoactive intestinal polypeptide, and secretin elicited a sustained increase in I sc. Responses to ATP and CCK were transient. Thus cultured guinea pig gallbladder epithelia display the range of responses observed in the native tissue and are an appropriate model for studies of ion transport in gallbladder and intestinal epithelia.

Antisecretory effects of berberine in rat ileum

1981 ◽  
Vol 241 (3) ◽  
pp. G253-G258 ◽  
Author(s):  
Y. H. Tai ◽  
J. F. Feser ◽  
W. G. Marnane ◽  
J. F. Desjeux
Keyword(s):  
Cyclic Amp ◽  
Adenylate Cyclase ◽  
Short Circuit ◽  
Short Circuit Current ◽  
Cyclase Activity ◽  
Adenylate Cyclase Activity ◽  
Rat Ileum ◽  
Ion Secretion ◽  
Stimulation Of

The in vitro antisecretory effects of the alkaloid berberine (1.0 mM) on intestinal ion secretion and mucosal adenylate cyclase and Na-K-ATPase activities were studied in the rat ileum. Mucosal berberine did not alter the individual basal net ion fluxes and basal adenylate cyclase activity but decreased short-circuit current (Isc) and increased the net absorption of chloride plus bicarbonate. In the cholera toxin-treated tissue, mucosal berberine stimulated absorption of Na and Cl and inhibited the increased adenylate cyclase activity but did not change the specific Na-K-ATPase activity, whereas serosal berberine stimulated Na secretion and decreased Isc. Mucosal berberine also decreased Isc, increased Cl permeability, and reversed the ion secretion induced by dibutyryl cyclic AMP, the heat-stable enterotoxin of Escherichia coli, and methylprednisolone administration. The antisecretory effects of mucosal berberine may be explained by stimulation of a Na-Cl-coupled absorptive transport process. The mechanism of action of serosal berberine remains to be elucidated. However, it is clear that mucosal berberine affects intestinal ion transport by mechanisms different from stimulation of the Na pump and probably at a step distal to the production or degradation of cyclic AMP or cyclic GMP.

Intestinal ion transport in NKCC1-deficient mice

2000 ◽  
Vol 279 (4) ◽  
pp. G707-G718 ◽  
Author(s):  
B. R. Grubb ◽  
E. Lee ◽  
A. J. Pace ◽  
B. H. Koller ◽  
R. C. Boucher
Keyword(s):  
Short Circuit ◽  
Basolateral Membrane ◽  
Short Circuit Current ◽  
Targeted Mutagenesis ◽  
Intestinal Epithelia ◽  
Entry Pathway ◽  
Intestinal Pathology ◽  
Ion Substitution ◽  
Deficient Mice ◽  
Intestinal Ion Transport

The Na+-K+-2Cl− cotransporter (NKCC1) located on the basolateral membrane of intestinal epithelia has been postulated to be the major basolateral Cl− entry pathway. With targeted mutagenesis, mice deficient in the NKCC1 protein were generated. The basal short-circuit current did not differ between normal and NKCC1 −/− jejuna. In the −/− jejuna, the forskolin response (22 μA/cm2; bumetanide insensitive) was significantly attenuated compared with the bumetanide-sensitive response (52 μA/cm2) in normal tissue. Ion-replacement studies demonstrated that the forskolin response in the NKCC1 −/− jejuna was HCO3 − dependent, whereas in the normal jejuna it was independent of the HCO3 − concentration in the buffer. NKCC1 −/− ceca exhibited a forskolin response that did not differ significantly from that of normal ceca, but unlike that of normal ceca, was bumetanide insensitive. Ion-substitution studies suggested that basolateral HCO3 − as well as Cl− entry (via non-NKCC1) paths played a role in the NKCC1 −/− secretory response. In contrast to cystic fibrosis mice, which lack both basal and stimulated Cl− secretion and exhibit severe intestinal pathology, the absence of intestinal pathology in NKCC1 −/− mice likely reflects the ability of the intestine to secrete HCO3 − and Cl− by basolateral entry mechanisms independent of NKCC1.

DCEBIO stimulates Cl−secretion in the mouse jejunum

2006 ◽  
Vol 290 (1) ◽  
pp. C152-C164 ◽  
Author(s):  
Kirk L. Hamilton ◽  
Matt Kiessling
Keyword(s):  
Steady State ◽  
Adenylate Cyclase ◽  
Short Circuit ◽  
Short Circuit Current ◽  
Dependent Manner ◽  
Steady State Response ◽  
Parent Molecule ◽  
Peak Response ◽  
State Response ◽  
Sustained Increase

We investigated the effects of 5,6-dichloro-1-ethyl-1,3-dihydro-2 H-benzimidazol-2-one(DCEBIO) on the Cl−secretory response of the mouse jejunum using the Ussing short-circuit current ( Isc) technique. DCEBIO stimulated a concentration-dependent, sustained increase in Isc(EC5041 ± 1 μM). Pretreating tissues with 0.25 μM forskolin reduced the concentration-dependent increase in Iscby DCEBIO and increased the EC50(53 ± 5 μM). Bumetanide blocked (82 ± 5%) the DCEBIO-stimulated Iscconsistent with Cl−secretion. DCEBIO was a more potent stimulator of Cl−secretion than its parent molecule, 1-ethyl-2-benzimidazolinone. Glibenclamide or NPPB reduced the DCEBIO-stimulated Iscby >80% indicating the participation of CFTR in the DCEBIO-stimulated Iscresponse. Clotrimazole reduced DCEBIO-stimulated Iscby 67 ± 15%, suggesting the participation of the intermediate conductance Ca2+-activated K+channel (IKCa) in the DCEBIO-activated Iscresponse. In the presence of maximum forskolin (10 μM), the DCEBIO response was reduced and biphasic, reaching a peak response of the change in Iscof 43 ± 5 μA/cm2and then falling to a steady-state response of 17 ± 10 μA/cm2compared with DCEBIO control tissues (61 ± 6 μA/cm2). The forskolin-stimulated Iscin the presence of DCEBIO was reduced compared with forskolin control tissues. Similar results were observed with DCEBIO and 8-BrcAMP where adenylate cyclase was bypassed. H89, a PKA inhibitor, reduced the DCEBIO-activated Isc, providing evidence that DCEBIO increased Cl−secretion via a cAMP/PKA-dependent manner. These data suggest that DCEBIO stimulates Cl−secretion of the mouse jejunum and that DCEBIO targets components of the Cl−secretory mechanism.

Cadmium-induced Inhibition of ADH-stimulated Ion Transport in Cultured Kidney-derived Epithelial Cells (A6)

1997 ◽  
Vol 25 (3) ◽  
pp. 271-277
Author(s):  
Henning F. Bjerregaard ◽  
Brian Faurskov
Keyword(s):  
Epithelial Cells ◽  
Adenylate Cyclase ◽  
Ion Transport ◽  
Hormonal Regulation ◽  
Short Circuit ◽  
Distal Tubule ◽  
Short Circuit Current ◽  
Epithelial Cell Line ◽  
Active Ion Transport ◽  
Camp Metabolism

An epithelial cell line (A6) derived from the distal tubule of toad kidney, was used to study the effect of cadmium (Cd2+) on the increase in active ion transport induced by antidiuretic hormone (ADH). Addition of Cd2+ (1mM) to the basolateral solution of A6 epithelia generated an immediate and transient increase in active ion transport, measured as short circuit current (SCC). This increase was not affected by prior addition of ADH. However, there was a distinct inhibition of ADH-induced stimulation of SCC in epithelia pre-treated with Cd2+. Since cAMP serves as an intracellular messenger for ADH by increasing the ion permeability of the apical membrane in A6 epithelial cells, the effects of Cd2+ on enzymes involved in cAMP metabolism were measured. The results showed that Cd2+ markedly inhibits cAMP production by inhibiting adenylate cyclase (which had been stimulated with forskolin, magnesium or a non-hydrolysed GTP-analog), indicating that Cd2+ inhibits the catalytic subunit of adenylate cyclase. Furthermore, degradation of cAMP by phosphodiesterase was not stimulated by Cd2+, also suggesting that the mechanism by which Cd2+ inhibits the ADH-induced ion transport could be through inhibition of adenylate cyclase. Taken together, these results indicate that, in addition to the well-known toxic effect on the proximal tubule, Cd2+ could also have an effect on the distal part of the kidney, where the important hormonal regulation of salt and water homeostasis takes place.

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