Paracellular transport refers to the transfer of substances across an

epithelium Epithelium or epithelial tissue is one of the four basic types of animal tissue, along with connective tissue, muscle tissue and nervous tissue. It is a thin, continuous, protective layer of compactly packed cells with a little intercellul ...

by passing through the intercellular space ''between'' the cells. It is in contrast to

transcellular transport Transcellular transport involves the transportation of solutes by a cell ''through'' a cell. Transcellular transport can occur in three different ways active transport, passive transport, and transcytosis. Active Transport Main article: Active ...

, where the substances travel ''through'' the cell, passing through both the apical membrane and

basolateral membrane Epithelial polarity is one example of the cell polarity that is a fundamental feature of many types of cells. Epithelial cells feature distinct 'apical', 'lateral' and 'basal' plasma membrane domains. Epithelial cells connect to one another via t ...

. The distinction has particular significance in

renal physiology Renal physiology (Latin ''rēnēs'', "kidneys") is the study of the physiology of the kidney. This encompasses all functions of the kidney, including maintenance of acid-base balance; regulation of fluid balance; regulation of sodium, potassium, ...

and intestinal physiology. Transcellular transport often involves energy expenditure whereas paracellular transport is unmediated and passive down a concentration gradient, or by

osmosis Osmosis (, ) is the spontaneous net movement or diffusion of solvent molecules through a selectively-permeable membrane from a region of high water potential (region of lower solute concentration) to a region of low water potential (region of ...

(for water) and

solvent drag A solvent (s) (from the Latin '' solvō'', "loosen, untie, solve") is a substance that dissolves a solute, resulting in a solution. A solvent is usually a liquid but can also be a solid, a gas, or a supercritical fluid. Water is a solvent for ...

for solutes. Paracellular transport also has the benefit that absorption rate is matched to load because it has no transporters that can be saturated. In most mammals, intestinal absorption of nutrients is thought to be dominated by transcellular transport, e.g., glucose is primarily absorbed via the

SGLT1 Sodium/glucose cotransporter 1 (SGLT1) also known as solute carrier family 5 member 1 is a protein in humans that is encoded by the gene which encodes the production of the SGLT1 protein to line the absorptive cells in the small intestine and th ...

transporter and other

glucose transporter Glucose transporters are a wide group of membrane proteins that facilitate the transport of glucose across the plasma membrane, a process known as facilitated diffusion. Because glucose is a vital source of energy for all life, these transporter ...

s. Paracellular absorption therefore plays only a minor role in glucose absorption, although there is evidence that paracellular pathways become more available when nutrients are present in the intestinal lumen. In contrast, small flying vertebrates (small birds and bats) rely on the paracellular pathway for the majority of glucose absorption in the intestine. This has been hypothesized to compensate for an evolutionary pressure to reduce mass in flying animals, which resulted in a reduction in intestine size and faster transit time of food through the gut. Capillaries of the blood–brain barrier have only transcellular transport, in contrast with normal capillaries which have both transcellular and paracellular transport. The paracellular pathway of transport is also important for the absorption of drugs in the

gastrointestinal tract The gastrointestinal tract (GI tract, digestive tract, alimentary canal) is the tract or passageway of the digestive system that leads from the mouth to the anus. The GI tract contains all the major organ (biology), organs of the digestive syste ...

. The paracellular pathway allows the permeation of hydrophilic molecules that are not able to permeate through the lipid membrane by the transcellular pathway of absorption. This is particularly important for hydrophilic pharmaceuticals, which may not have affinity for membrane-bound transporters, and therefore may be excluded from the transcellular pathway. The vast majority of drug molecules are transported through the transcellular pathway, and the few which rely on the paracellular pathway of transportation typically have a much lower bioavailability; for instance,

levothyroxine Levothyroxine, also known as -thyroxine, is a manufactured form of the thyroid hormone thyroxine (T4). It is used to treat thyroid hormone deficiency (hypothyroidism), including a severe form known as myxedema coma. It may also be used to tre ...

has an

oral bioavailability In pharmacology, bioavailability is a subcategory of absorption and is the fraction (%) of an administered drug that reaches the systemic circulation. By definition, when a medication is administered intravenously, its bioavailability is 100 ...

of 40 to 80%, and

desmopressin Desmopressin, sold under the trade name DDAVP among others, is a medication used to treat diabetes insipidus, bedwetting, hemophilia A, von Willebrand disease, and high blood urea levels. In hemophilia A and von Willebrand disease, it should on ...

of 0.16%.

Structure of paracellular channels

Some

claudin Claudins are a family of proteins which, along with occludin, are the most important components of the tight junctions ( zonulae occludentes). Tight junctions establish the paracellular barrier that controls the flow of molecules in the interce ...

s form

tight junction Tight junctions, also known as occluding junctions or ''zonulae occludentes'' (singular, ''zonula occludens''), are multiprotein junctional complexes whose canonical function is to prevent leakage of solutes and water and seals between the epith ...

-associated pores that allow paracellular ion transport. The tight junctions have a net negative charge, and are believed to preferentially transport positively charged molecules. Tight junctions in the intestinal epithelium are also known to be size-selective, such that large molecules (with molecular radii greater than about 4.5 Å) are excluded. Larger molecules may also pass the intestinal epithelium via the paracellular pathway, although at a much slower rate and the mechanism of this transport via a "leak" pathway is unknown but may include transient breaks in the epithelial barrier. Paracellular transport can be enhanced through the displacement of zona occludens proteins from the junctional complex by the use of permeation enhancers. Such enhancers include medium chain fatty acids (e.g. capric acid), chitosans, zona occludens toxin, etc.

References

{{reflist, 30em Cell biology