scholarly journals Intestinal TMEM16A control luminal chloride secretion in a NHERF1 dependent manner

2021 ◽  
Vol 25 ◽  
pp. 100912
Author(s):  
Tultul Saha ◽  
Joydeep Aoun ◽  
Mikio Hayashi ◽  
Sheikh Irshad Ali ◽  
Paramita Sarkar ◽  
...  
Keyword(s):  
Chloride Secretion ◽  
Dependent Manner

Chloride secretion and conductance of teleost opercular membrane: effects of prolactin

1982 ◽  
Vol 242 (3) ◽  
pp. R380-R389 ◽  
Author(s):  
J. K. Foskett ◽  
T. E. Machen ◽  
H. A. Bern
Keyword(s):  
Active Transport ◽  
Short Circuit ◽  
Chloride Secretion ◽  
Alternative Interpretation ◽  
Chloride Cells ◽  
Dependent Manner ◽  
Transport Pathway ◽  
Accurate Analysis ◽  
Equivalent Circuit Analysis ◽  
Fish Yield

Effects of prolactin on transport properties of opercular membranes from seawater-adapted tilapia, Sarotherodon mossambicus, have been examined. These membranes are high conductance (average Gt approximately 4 mS.cm-2) tissues with short-circuit currents (I) equal to net chloride secretion. Despite high Gt, nonlinear current-voltage relationships suggest that opercular membranes cannot be classified as "leaky" tissues. Variability among membranes is reflected in a linear relationship between I and Gt with a slope equal to 26 mV and the zero-current Gt intercept equal to 0.45 mS.cm-2. Prolactin injections decrease I and Gt in a dose-dependent manner. Phosphodiesterase inhibition, without effect on I in untreated fish, often partially reverses these prolactin effects. Gt-I data from prolactin-treated fish yield a slope of 18 mV and a Gt intercept of 0.10 mS.cm-2. The effects of prolactin are discussed in terms of conventional equivalent circuit analysis. Discrepancies between predictions based on this model and the actual data indicate that an alternative interpretation, based on a heterogeneous cell population, is more accurate. Analysis of this circuit suggests that the ratio of paracellular to active transport pathway conductances associated with chloride cells is constant and that differences in Gt and I are due to parallel changes in these conductances. Prolactin may effectively "remove" chloride cells from these membranes as well as inhibit (reversible by elevated cellular cAMP levels) active transport pathway conductance of remaining cells.

Functional characterization and expression of PBR in rat gastric mucosa: stimulation of chloride secretion by PBR ligands

2004 ◽  
Vol 286 (6) ◽  
pp. G1069-G1080 ◽  
Author(s):  
M. A. Ostuni ◽  
K. Marazova ◽  
G. Peranzi ◽  
B. Vidic ◽  
V. Papadopoulos ◽  
...  
Keyword(s):  
Gastric Mucosa ◽  
Short Circuit ◽  
Functional Characterization ◽  
Benzodiazepine Receptor ◽  
Chloride Secretion ◽  
Parietal Cells ◽  
Receptor Protein ◽  
Antral Mucosa ◽  
Dependent Manner ◽  
Calcium Depletion

Previous studies have demonstrated that gastric mucosa contained high levels of the polypeptide diazepam binding inhibitor, the endogenous ligand of the peripheral-type benzodiazepine receptor (PBR). However, the expression and function of this receptor protein in these tissues have not been investigated. Immunohistochemistry identified an intense PBR immunoreactivity in the mucous and parietal cells of rat gastric fundus and in the mucous cells of antrum. Immunoelectron microscopy revealed the mitochondrial localization of PBR in these cells. Binding of isoquinoline PK 11195 and benzodiazepine Ro5–4864 to gastric membranes showed that fundus had more PBR-binding sites than antrum, displaying higher affinity for PK 11195 than Ro5–4864. In a Ussing chamber, PK 11195 and Ro5–4864 increased short-circuit current ( Isc) in fundic and antral mucosa in a concentration-dependent manner in the presence of GABAA and central benzodiazepine receptor (CBR) blockers. This increase in Isc was abolished after external Cl− substitution and was sensitive to chloride channels or transporter inhibitors. PK 11195-induced chloride secretion was also 1) sensitive to verapamil and extracellular calcium depletion, 2) blocked by thapsigargin and intracellular calcium depletion, and 3) abolished by the mitochondrial pore transition complex inhibitor cyclosporine A. PK 11195 had no direct effect on H+ secretion, indicating that it stimulates a component of Cl− secretion independent of acid secretion in fundic mucosa. These data demonstrate that mucous and parietal cells of the gastric mucosa express mitochondrial PBR functionally coupled to Ca2+-dependent Cl− secretion, possibly involved in the gastric mucosa protection.

Antagonists of epithelial chloride channels inhibit cAMP synthesis

1991 ◽  
Vol 69 (4) ◽  
pp. 501-506 ◽  
Author(s):  
S. Heisler
Keyword(s):  
Vasoactive Intestinal Polypeptide ◽  
Chloride Channels ◽  
Chloride Transport ◽  
Chloride Secretion ◽  
Channel Blockers ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Camp Synthesis ◽  
Camp Formation ◽  
Intestinal Polypeptide

In past studies we observed that the chloride channel blocker, diphenylamine-2-carboxylate (DPC) and chemically related drugs (Hoechst compounds 131, 143, 144) inhibited cAMP formation in mouse pituitary tumor cells. The object of this study was to determine whether these drugs inhibited chloride transport in human T-84 colonic carcinoma cells through an effect on cAMP metabolism. Chloride secretion (measured as 125I efflux from isotope-preloaded cells) was stimulated in a concentration-dependent manner by vasoactive intestinal polypeptide (VIP) (EC50 = 1.5 × 10−10 M) which similarly increased cAMP synthesis (EC50 = 1.6 × 10−8 M). The cAMP response to VIP was inhibited 17, 52, 55, and 78% maximally by DPC and compounds 144, 143, and 131, respectively. In untreated T-84 cells, 125I secretion fell by 66% after 3 min; VIP (10−7 M) increased secretion about fivefold over the same period. Both basal and VIP-stimulated 125I secretion were inhibited up to 60% by compound 131. Pretreatment of cells with pertussis toxin did not attenuate the inhibitory effect of channel blockers on either VIP-stimulated cAMP synthesis or 125I secretion. The cationophore, A-23187, which had no effect on cAMP formation, and 8-Br-cAMP both stimulated 125I secretion from T-84 cells. These secretory responses were inhibited by compound 131. The mechanism by which phenylanthranilic acids antagonize cAMP synthesis and its significance is not known; however, the data suggest that this family of drugs may inhibit chloride transport by both cAMP-dependent and independent mechanisms.Key words: T-84 cells, chloride secretion, vasoactive intestinal polypeptide, diphenylamine-2-carboxylate, inhibition of cyclic AMP synthesis.

scholarly journals Glucagon-like peptide-1 modulates neurally evoked mucosal chloride secretion in guinea pig small intestine in vitro

2012 ◽  
Vol 302 (3) ◽  
pp. G352-G358 ◽  
Author(s):  
Sara Baldassano ◽  
Guo-Du Wang ◽  
Flavia Mulè ◽  
Jackie D. Wood
Keyword(s):  
Small Intestine ◽  
Guinea Pig ◽  
Receptor Antagonist ◽  
Vasoactive Intestinal Peptide ◽  
Short Circuit ◽  
Chloride Secretion ◽  
Dependent Manner ◽  
Evoked Responses ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

Glucagon-like peptide-1 (GLP-1) acts at the G protein-coupled receptor, GLP-1R, to stimulate secretion of insulin and to inhibit secretion of glucagon and gastric acid. Involvement in mucosal secretory physiology has received negligible attention. We aimed to study involvement of GLP-1 in mucosal chloride secretion in the small intestine. Ussing chamber methods, in concert with transmural electrical field stimulation (EFS), were used to study actions on neurogenic chloride secretion. ELISA was used to study GLP-1R effects on neural release of acetylcholine (ACh). Intramural localization of GLP-1R was assessed with immunohistochemistry. Application of GLP-1 to serosal or mucosal sides of flat-sheet preparations in Ussing chambers did not change baseline short-circuit current ( Isc), which served as a marker for chloride secretion. Transmural EFS evoked neurally mediated biphasic increases in Iscthat had an initial spike-like rising phase followed by a sustained plateau-like phase. Blockade of the EFS-evoked responses by tetrodotoxin indicated that the responses were neurally mediated. Application of GLP-1 reduced the EFS-evoked biphasic responses in a concentration-dependent manner. The GLP-1 receptor antagonist exendin-(9–39) suppressed this action of GLP-1. The GLP-1 inhibitory action on EFS-evoked responses persisted in the presence of nicotinic or vasoactive intestinal peptide receptor antagonists but not in the presence of a muscarinic receptor antagonist. GLP-1 significantly reduced EFS-evoked ACh release. In the submucosal plexus, GLP-1R immunoreactivity (IR) was expressed by choline acetyltransferase-IR neurons, neuropeptide Y-IR neurons, somatostatin-IR neurons, and vasoactive intestinal peptide-IR neurons. Our results suggest that GLP-1R is expressed in guinea pig submucosal neurons and that its activation leads to a decrease in neurally evoked chloride secretion by suppressing release of ACh at neuroepithelial junctions in the enteric neural networks that control secretomotor functions.

Hydrogen peroxide stimulates chloride secretion in primary inner medullary collecting duct cells via mPGES-1-derived PGE2

2007 ◽  
Vol 293 (5) ◽  
pp. F1571-F1576 ◽  
Author(s):  
Sunhapas Soodvilai ◽  
Zhanjun Jia ◽  
Tianxin Yang
Keyword(s):  
Collecting Duct ◽  
Short Circuit ◽  
Ussing Chamber ◽  
Short Circuit Current ◽  
Chloride Secretion ◽  
Dependent Manner ◽  
Semipermeable Membranes ◽  
Nacl Transport ◽  
Inner Medullary Collecting Duct ◽  
Medullary Collecting Duct

We investigated the role and mechanism of H2O2 in regulation of NaCl transport in primary inner medullary collecting duct (IMCD) cells. IMCD cells were isolated from wild-type mice and grown onto semipermeable membranes, and short-circuit current ( Isc) was determined by Ussing chamber. Exposure of IMCD cells to H2O2 at a range of 100–300 μM caused a rapid increase in Isc in a time- and dose-dependent manner. This increase was almost abolished by the cystic fibrosis transmembrane conductance regulator (CFTR) Cl− channel inhibitors diphenylamine-2-carboxylic acid (DPC) and CFTRinhibitor-172. In contrast, the magnitude of stimulation was unaffected by the epithelial Na+ channel (ENaC) inhibitor amiloride. The H2O2-induced Cl− secretion was significantly inhibited by indomethacin, as well as by microsomal PGE synthase-1 (mPGES-1) deficiency. Like H2O2, PGE2 treatment induced a twofold increase in Isc that was reduced by the protein kinase A (PKA) inhibitors H-89 and KT5720. These data suggest that H2O2 stimulates CFTR Cl− channel-mediated Cl− secretion through cyclooxygenase- and mPGES-1-dependent release of PGE2 and subsequent activation of PKA.

Water and enzyme secretion are tightly coupled in pancreatic secretion stimulated by food or CCK-58 but not by CCK-8

2005 ◽  
Vol 288 (5) ◽  
pp. G866-G879 ◽  
Author(s):  
M. Yamamoto ◽  
J. R. Reeve ◽  
D. A. Keire ◽  
G. M. Green
Keyword(s):  
Protein Secretion ◽  
Pancreatic Secretion ◽  
Chloride Secretion ◽  
Enzyme Secretion ◽  
Dependent Manner ◽  
Two Component ◽  
Tightly Coupled ◽  
Water Secretion ◽  
Basal Phase ◽  
Protein Output

Pancreatic secretion of protein, water, chloride, and bicarbonate under basal conditions and in response to intravenous and intraduodenal stimuli were studied in awake rats fully recovered from surgery. During the basal phase of pancreatic secretion, protein output and water output were weakly correlated or uncorrelated, consistent with separate regulation and distinct cellular origin of enzyme (acinar cells) and water (duct cells), referred to as the two-component paradigm of pancreatic secretion. When pancreatic secretion was stimulated physiologically, water and protein output abruptly became strongly and significantly correlated, suggesting that protein secretion and water secretion are tightly coupled or that protein secretion is dependent on water secretion. The apparent function of this coupling is to resist or prevent increases in protein concentration as protein output increases. This pattern of secretion was reproduced by intravenous infusion of the CCK-58 form of cholecystokinin, which strongly stimulates pancreatic water and chloride secretion, but not by CCK-8, which only weakly stimulates water and chloride secretion in a non-dose-dependent manner. The remarkably tight association of water and protein secretion in food-stimulated and CCK-58-stimulated pancreatic secretion is consistent with a single cell type as the origin of both water and enzyme secretion, i.e., the acinar cell, and is not consistent with the two-component paradigm of pancreatic secretion. Because CCK-58 is the only detectable endocrine form of cholecystokinin in the rat and its bioactivity pattern is markedly and qualitatively different from CCK-8, actions previously recorded for CCK-8 should be reexamined.

scholarly journals Glucagon-like peptide-2 modulates neurally evoked mucosal chloride secretion in guinea pig small intestine in vitro

2009 ◽  
Vol 297 (4) ◽  
pp. G800-G805 ◽  
Author(s):  
Sara Baldassano ◽  
Sumei Liu ◽  
Mei-Hu Qu ◽  
Flavia Mulè ◽  
Jackie D. Wood
Keyword(s):  
Guinea Pig ◽  
Vasoactive Intestinal Peptide ◽  
Acetylcholine Release ◽  
Short Circuit ◽  
Chloride Secretion ◽  
Dependent Manner ◽  
Evoked Responses ◽  
Guinea Pig Ileum ◽  
Ussing Chambers ◽  
Glucagon Like Peptide

Glucagon-like peptide-2 (GLP-2) is an important neuroendocrine peptide in intestinal physiology. It influences digestion, absorption, epithelial growth, motility, and blood flow. We studied involvement of GLP-2 in intestinal mucosal secretory behavior. Submucosal-mucosal preparations from guinea pig ileum were mounted in Ussing chambers for measurement of short-circuit current ( Isc) as a surrogate for chloride secretion. GLP-2 action on neuronal release of acetylcholine was determined with ELISA. Enteric neuronal expression of the GLP-2 receptor (GLP-2R) was studied with immunohistochemical methods. Application of GLP-2 (0.1–100 nM) to the serosal or mucosal side of the preparations evoked no change in baseline Isc and did not alter transepithelial ionic conductance. Transmural electrical field stimulation (EFS) evoked characteristic biphasic increases in Isc, with an initially rapid rising phase followed by a sustained phase. Application of GLP-2 reduced the EFS-evoked biphasic responses in a concentration-dependent manner. The GLP-2R antagonist GLP-2-(3-33) significantly reversed suppression of the EFS-evoked responses by GLP-2. Tetrodotoxin, scopolamine, and hexamethonium, but not vasoactive intestinal peptide type 1 receptor (VPAC1) antagonist abolished or reduced to near zero the EFS-evoked responses. GLP-2 suppressed EFS-evoked acetylcholine release as measured by ELISA. Pretreatment with GLP-2-(3-33) offset this action of GLP-2. In the submucosal plexus, GLP-2R immunoreactivity (-IR) was expressed in choline acetyltransferase-IR neurons, somatostatin-IR neurons, neuropeptide Y-IR neurons, and vasoactive intestinal peptide-IR neurons. We conclude that submucosal neurons in the guinea pig ileum express GLP-2R. Activation of GLP-2R decreases neuronally evoked epithelial chloride secretion by suppressing acetylcholine release from secretomotor neurons.

Tyrosine phosphorylation is a novel pathway for regulation of chloride secretion in shark rectal gland

1995 ◽  
Vol 269 (4) ◽  
pp. F594-F600 ◽  
Author(s):  
R. W. Lehrich ◽  
J. N. Forrest
Keyword(s):  
Tyrosine Phosphorylation ◽  
Kinase Inhibitor ◽  
Chloride Transport ◽  
Short Circuit ◽  
Chloride Secretion ◽  
Rectal Gland ◽  
Dependent Manner ◽  
Camp Content ◽  
Tubular Cells ◽  
Genistein Treatment

We used the specific tyrosine kinase inhibitor genistein to define the involvement of tyrosine phosphorylation in the regulation of chloride transport in the rectal gland of the dogfish shark, a model for chloride secretion via a cystic fibrosis transmembrane conductance regulator (CFTR)-like channel. In the perfused gland, genistein (100 microM) promptly increased chloride secretion from basal values of 159 +/- 36 to 966 +/- 49 mueq.h-1.g-1 (P < 0.0001). Bumentanide fully reversed genistein-induced secretion. In primary culture monolayers of rectal gland tubular cells, genistein, but not the inactive 7-glucoside form, genistin, increased short-circuit current in a dose-dependent manner, from basal values of 2.7 +/- 4.3 to 104 +/- 10 microA/cm2 (P < 0.0001). Apically applied genistein induced significantly greater chloride secretion than basolateral addition. Genistein did not increase the adenosine 3',5'-cyclic monophosphate (cAMP) content of either perfused glands or cultured monolayers. Using an anti-phosphotyrosine antibody, we observed phosphorylation of multiple proteins. Four peptides, with molecular masses of 250, 210, 55, and 53 kDa, responded to genistein treatment with a decrease in tyrosine phosphorylation. These data demonstrate the following: 1) genistein induces bumetanide-sensitive chloride secretion in both perfused rectal glands and cultured tubular cells; 2) these effects are not accompanied by an elevation of tissue cAMP, indicating that genistein-induced secretion is not mediated by the cAMP-protein kinase A pathway; and 3) genistein-sensitive peptides are present in the rectal gland cell and are candidates for involvement in the regulation of chloride secretion.(ABSTRACT TRUNCATED AT 250 WORDS)

Action of pituitary adenylate cyclase-activating polypeptide on ion transport in guinea pig distal colon

1993 ◽  
Vol 264 (3) ◽  
pp. G433-G441 ◽  
Author(s):  
A. Kuwahara ◽  
Y. Kuwahara ◽  
T. Mochizuki ◽  
N. Yanaihara
Keyword(s):  
Adenylate Cyclase ◽  
Guinea Pig ◽  
Ion Transport ◽  
Short Circuit ◽  
Distal Colon ◽  
Chloride Secretion ◽  
Dependent Manner ◽  
Evoked Responses ◽  
Concentration Dependent Manner ◽  
Pituitary Adenylate Cyclase

The aim of the present study was to investigate the action of pituitary adenylate cyclase-activating polypeptide (PACAP) on ion transport in the guinea pig distal colon. Submucosal/mucosal segments from distal colon were mounted in Ussing flux chambers, and increases in short-circuit current (Isc) were used as an index of secretion. Serosal addition of PACAP-38 and PACAP-27 produced concentration-dependent (10(-10)-10(-6) M) increases in Isc. Furosemide and chloride-free solutions significantly reduced the PACAP-evoked responses. Tetrodotoxin (TTX) completely blocked PACAP-evoked responses. Atropine significantly reduced the PACAP-evoked responses but did not abolish the responses. The results suggest that PACAP evokes chloride secretion through cholinergic and noncholinergic neural mechanism. Vasoactive intestinal polypeptide (VIP), peptide histidine-isoleucine amide, and helodermin evoked Isc in a concentration-dependent manner. Atropine reduced but did not abolish the VIP- and related peptides-evoked responses. TTX also significantly decreased the responses to higher concentrations of VIP and related peptides but did not abolish the responses. The results suggest that VIP and related peptides act on both submucosal neurons and the epithelial cell itself. VIP tachyphylaxis significantly decreased PACAP-38- and PACAP-27-evoked responses. These results provide evidence that PACAP recognizes, in some part, VIP receptors in the submucosal neurons to evoke chloride secretion.

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