100:. 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,
90:. 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.
131:
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
136:) 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.
139:
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.
613:
Chediack JG, Caviedes-Vidal E, Fasulo V, Yamin LJ, Karasov WH (April 2003). "Intestinal passive absorption of water-soluble compounds by sparrows: effect of molecular size and luminal nutrients".
71:
and intestinal physiology. Transcellular transport often involves energy expenditure whereas paracellular transport is unmediated and passive down a concentration gradient, or by
93:
Capillaries of the blood–brain barrier have only transcellular transport, in contrast with normal capillaries which have both transcellular and paracellular transport.
268:
323:
Pappenheimer JR, Reiss KZ (1987). "Contribution of solvent drag through intercellular junctions to absorption of nutrients by the small intestine of the rat".
82:
In most mammals, intestinal absorption of nutrients is thought to be dominated by transcellular transport, e.g., glucose is primarily absorbed via the
79:
for solutes. Paracellular transport also has the benefit that absorption rate is matched to load because it has no transporters that can be saturated.
179:
198:
252:
156:
411:"Paracellular nutrient absorption is higher in bats than rodents: integrating from intact animals to the molecular level"
707:"The digestive adaptation of flying vertebrates: high intestinal paracellular absorption compensates for smaller guts"
462:"The digestive adaptation of flying vertebrates: high intestinal paracellular absorption compensates for smaller guts"
221:
519:
Price ER, Brun A, Caviedes-Vidal E, Karasov WH (January 2015). "Digestive adaptations of aerial lifestyles".
49:
31:
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Hall, John E. (2020). "Passive Water
Reabsorption by Osmosis Coupled Mainly to Sodium Reabsorption".
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Caviedes-Vidal E, McWhorter TJ, Lavin SR, Chediack JG, Tracy CR, Karasov WH (November 2007).
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Caviedes-Vidal E, McWhorter TJ, Lavin SR, Chediack JG, Tracy CR, Karasov WH (November 2007).
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658:"The role of molecular remodeling in differential regulation of tight junction permeability"
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The paracellular pathway of transport is also important for the absorption of drugs in the
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Journal of
Comparative Physiology B: Biochemical, Systemic, and Environmental Physiology
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284:"Paracellular intestinal transport of six-carbon sugars is negligible in the rat"
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Proceedings of the
National Academy of Sciences of the United States of America
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Proceedings of the
National Academy of Sciences of the United States of America
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Lavin SR, Karasov WH (2008). "Allometry of paracellular absorption in birds".
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Turner JR, Buschmann MM, Romero-Calvo I, Sailer A, Shen L (December 2014).
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Price ER, Rott KH, Caviedes-Vidal E, Karasov WH (October 2014).
228:. Department of Physiology. Kuwait University. Archived from
27:
Transfer of substances by passing through space between cells
128:-associated pores that allow paracellular ion transport.
199:"Transport Across a Cell Layer: Transcellular Transport"
282:Schwartz RM, Furne JK, Levitt MD (October 1995).
566:"Physiology and function of the tight junction"
67:The distinction has particular significance in
40:refers to the transfer of substances across an
245:Guyton and Hall textbook of medical physiology
8:
662:Seminars in Cell & Developmental Biology
564:Anderson JM, Van Itallie CM (August 2009).
44:by passing through the intercellular space
30:For the complementary transport route, see
570:Cold Spring Harbor Perspectives in Biology
267:: CS1 maint: location missing publisher (
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368:Physiological and Biochemical Zoology
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182:. Trinity University. Archived from
180:"Epithelial Transcellular Transport"
415:The Journal of Experimental Biology
56:the cell, passing through both the
247:(Fourteenth ed.). Amsterdam.
226:Renal Physiology Tutorial Web Site
116:Structure of paracellular channels
25:
48:the cells. It is in contrast to
325:The Journal of Membrane Biology
203:Essentials of Human Physiology
52:, where the substances travel
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674:10.1016/j.semcdb.2014.09.022
301:10.1016/0016-5085(95)90580-4
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627:10.1007/s00360-002-0314-8
732:10.1073/pnas.0703159104
487:10.1073/pnas.0703159104
163:. Bayer. Archived from
50:transcellular transport
32:Transcellular transport
98:gastrointestinal tract
86:transporter and other
38:Paracellular transport
421:(Pt 19): 3483–3492.
232:on 14 February 2006.
157:"Calcium Adsorption"
106:oral bioavailability
88:glucose transporters
62:basolateral membrane
723:2007PNAS..10419132C
717:(48): 19132–19137.
478:2007PNAS..10419132C
472:(48): 19132–19137.
222:"Tubular Transport"
186:on 9 February 2007.
428:10.1242/jeb.105619
337:10.1007/BF02209145
108:of 40 to 80%, and
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521:Physiology
197:Nosek TM.
144:References
112:of 0.16%.
42:epithelium
263:cite book
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