Page last updated: 2024-10-24

transepithelial chloride transport

Definition

Target type: biologicalprocess

The directed movement of chloride ions from one side of an epithelium to the other. [GOC:mah]

Transepithelial chloride transport is a fundamental process in many tissues, particularly in the gastrointestinal, respiratory, and renal systems. It involves the movement of chloride ions across epithelial cell layers, which are tightly connected by specialized junctions. This process is crucial for maintaining fluid balance, regulating electrolyte concentrations, and ensuring proper organ function. The movement of chloride ions occurs through a complex interplay of active and passive transport mechanisms.

The active transport of chloride ions is driven by the action of specific membrane proteins. The primary transporter responsible for chloride secretion is the cystic fibrosis transmembrane conductance regulator (CFTR), a chloride channel regulated by ATP binding and phosphorylation. CFTR is expressed in various epithelial tissues, including the airway, pancreas, and intestine. When activated, CFTR opens and allows chloride ions to flow out of the cell down their electrochemical gradient.

In addition to CFTR, other active transporters contribute to transepithelial chloride transport. These include the Na+/K+/2Cl- cotransporter (NKCC) and the K+/Cl- cotransporter (KCC). NKCC transports chloride ions into the cell along with sodium and potassium, while KCC facilitates the movement of chloride ions out of the cell.

The passive transport of chloride ions across epithelial cell layers is primarily mediated by chloride channels. These channels are present in both the apical and basolateral membranes of epithelial cells. The apical membrane, facing the lumen, often contains channels like CFTR, which are regulated by intracellular signaling pathways. The basolateral membrane, facing the interstitial fluid, typically expresses other types of chloride channels, including calcium-activated chloride channels (CaCC) and volume-regulated anion channels (VRAC).

Transepithelial chloride transport is tightly regulated by a variety of factors, including intracellular signaling pathways, hormonal cues, and environmental stimuli. For example, changes in intracellular calcium levels, cyclic AMP (cAMP) concentrations, and the activation of various kinases can modulate the activity of chloride channels and transporters. Hormones such as aldosterone and vasopressin can also influence transepithelial chloride transport by altering the expression and activity of specific transport proteins.

Dysregulation of transepithelial chloride transport can lead to various pathological conditions. For instance, mutations in the CFTR gene result in cystic fibrosis, a genetic disorder characterized by impaired chloride secretion in various tissues, leading to mucus buildup and organ dysfunction. Other disorders affecting transepithelial chloride transport include secretory diarrhea, dehydration, and electrolyte imbalances.

In summary, transepithelial chloride transport is a complex and tightly regulated process involving both active and passive mechanisms. This process is crucial for maintaining fluid balance, regulating electrolyte concentrations, and ensuring proper organ function. Dysregulation of this process can lead to various pathological conditions.'
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Proteins (3)

ProteinDefinitionTaxonomy
P2Y purinoceptor 6A P2Y purinoceptor 6 that is encoded in the genome of human. [PRO:WCB, UniProtKB:Q15077]Homo sapiens (human)
Solute carrier family 12 member 2A solute carrier family 12 member 2 that is encoded in the genome of human. [PRO:DNx, UniProtKB:P55011]Homo sapiens (human)
P2Y purinoceptor 4A P2Y purinoceptor 4 that is encoded in the genome of human. [PRO:WCB, UniProtKB:P51582]Homo sapiens (human)

Compounds (22)

CompoundDefinitionClassesRoles
bumetanideamino acid;
benzoic acids;
sulfonamide
diuretic;
EC 3.6.3.49 (channel-conductance-controlling ATPase) inhibitor
pyridoxal phosphate-6-azophenyl-2',4'-disulfonic acid5'-phosphopyridoxal-6-azobenzene-2,4-disulfonic acid : An arenesulfonic acid that is pyridoxal 5'-phosphate carrying an additional 2,4-disulfophenylazo substituent at position 6.

pyridoxal phosphate-6-azophenyl-2',4'-disulfonic acid: a novel antagonist that selectively blocks P2 purinoceptor receptors; a useful tool to study co-transmission in tissues when ATP and coexisting neurotransmitters act in concert
arenesulfonic acid;
azobenzenes;
methylpyridines;
monohydroxypyridine;
organic phosphate;
pyridinecarbaldehyde
purinergic receptor P2X antagonist
suraminsuramin : A member of the class of phenylureas that is urea in which each of the amino groups has been substituted by a 3-({2-methyl-5-[(4,6,8-trisulfo-1-naphthyl)carbamoyl]phenyl}carbamoyl)phenyl group. An activator of both the rabbit skeletal muscle RyR1 and sheep cardiac RyR2 isoform ryanodine receptor channels, it has been used for the treatment of human African trypanosomiasis for over 100 years.

Suramin: A polyanionic compound with an unknown mechanism of action. It is used parenterally in the treatment of African trypanosomiasis and it has been used clinically with diethylcarbamazine to kill the adult Onchocerca. (From AMA Drug Evaluations Annual, 1992, p1643) It has also been shown to have potent antineoplastic properties.
naphthalenesulfonic acid;
phenylureas;
secondary carboxamide
angiogenesis inhibitor;
antinematodal drug;
antineoplastic agent;
apoptosis inhibitor;
EC 2.7.11.13 (protein kinase C) inhibitor;
GABA antagonist;
GABA-gated chloride channel antagonist;
purinergic receptor P2 antagonist;
ryanodine receptor agonist;
trypanocidal drug
adenosine diphosphateAdenosine Diphosphate: Adenosine 5'-(trihydrogen diphosphate). An adenine nucleotide containing two phosphate groups esterified to the sugar moiety at the 5'-position.adenosine 5'-phosphate;
purine ribonucleoside 5'-diphosphate
fundamental metabolite;
human metabolite
uridine diphosphateUridine Diphosphate: A uracil nucleotide containing a pyrophosphate group esterified to C5 of the sugar moiety.pyrimidine ribonucleoside 5'-diphosphate;
uridine 5'-phosphate
Escherichia coli metabolite;
mouse metabolite
cytidine diphosphateCytidine Diphosphate: Cytidine 5'-(trihydrogen diphosphate). A cytosine nucleotide containing two phosphate groups esterified to the sugar moiety. Synonyms: CRPP; cytidine pyrophosphate.cytidine 5'-phosphate;
pyrimidine ribonucleoside 5'-diphosphate
Escherichia coli metabolite;
mouse metabolite
uridine triphosphateUridine Triphosphate: Uridine 5'-(tetrahydrogen triphosphate). A uracil nucleotide containing three phosphate groups esterified to the sugar moiety.pyrimidine ribonucleoside 5'-triphosphate;
uridine 5'-phosphate
Escherichia coli metabolite;
mouse metabolite
uridine diphosphate glucoseUDP-alpha-D-glucose : The alpha-anomer of UDP-alpha-D-glucose. It is used in nucleotide sugars metabolism.

Uridine Diphosphate Glucose: A key intermediate in carbohydrate metabolism. Serves as a precursor of glycogen, can be metabolized into UDPgalactose and UDPglucuronic acid which can then be incorporated into polysaccharides as galactose and glucuronic acid. Also serves as a precursor of sucrose lipopolysaccharides, and glycosphingolipids.
UDP-D-glucosefundamental metabolite
diquafosoldiquafosol: purinoceptor P2Y(2) receptor agonist

P(1),P(4)-bis(uridin-5'-yl) tetraphosphate : A pyrimidine ribonucleoside 5'-tetraphosphate compound having 5'-uridinyl residues at the P(1)- and P(4)-positions.
pyrimidine ribonucleoside 5'-tetraphosphate;
uridine 5'-phosphate
mouse metabolite;
P2Y2 receptor agonist
phosphoribofuranosylbarbituric acid
uridine 5'-tetraphosphate
TTPpyrimidine ribonucleoside 5'-triphosphate
4-thiouridine triphosphate
2-methylthio-atp2-methylthio-ATP: purinergic receptors agonist; relaxes mammalian gut preparations; structure given in first source
n-(4-methylthiazol-2-yl)-2-(6-phenylpyridazin-3-ylthio)acetamideN-(4-methylthiazol-2-yl)-2-(6-phenylpyridazin-3-ylthio)acetamide: a KCC2 cotransporter antagonistpyridazines;
ring assembly
5-bromouridine triphosphate5-bromouridine 5'-triphosphate : A pyrimidine ribonucleoside 5'-triphosphate having 5-bromouracil as the pyrimidine component.organobromine compound;
pyrimidine ribonucleoside 5'-triphosphate
denufosol tetrasodium
denufosol tetrasodiumdenufosol tetrasodium: for treatment of cystic fibrosis
5-fluorouridine 5'-triphosphate
4-thiouridylic acid
acid blue 25
guanosine diphosphateGuanosine Diphosphate: A guanine nucleotide containing two phosphate groups esterified to the sugar moiety.guanosine 5'-phosphate;
purine ribonucleoside 5'-diphosphate
Escherichia coli metabolite;
mouse metabolite;
uncoupling protein inhibitor