Intestinal Electrolyte Secretion

Abstract

The contemporary paradigm for active chloride secretion by vertebrate epithelial cells evolved, at least in part, from experiments that began in the laboratory of Dr William Silen at Beth Israel Hospital in Boston, Mass. It was first shown there that cyclic adenosine monophosphate and cholera toxin stimulate active chloride secretion when added to intestinal mucosa in vitro. The paradigm, which evolved further from experiments on shark rectal gland and flounder intestine at the Mt Desert Island Biological Laboratory in Salsbury Cove, Maine, is as follows: Chloride enters some epithelial cells by sodium-potassium-chloride cotransport with a stoichiometry of 1:1:2 and accumulates intracellularly because of the sodium gradient maintained by sodium-potassium-adenosinetriphosphatase in the basolateral membrane; the chloride is then released from the cell through chloride channels in the membrane opposite that of the cotransporter. If the cotransporter is basolateral and the channel is apical, chloride is secreted; if it is the other way around, chloride is absorbed. In a number of secretory epithelial cells, cyclic adenosine monophosphate activates these channels, thereby initiating secretion. A defect in the activation of these channels by cyclic adenosine monophosphate is the root cause of cystic fibrosis.

Molecular Mechanisms of Disturbed Electrolyte Transport in Intestinal Inflammation

“…measured the rectal PD in UC patients sequentially and found that the rectal PD became positive during acute flare‐ups, followed by recovery to negative values during the healing phase 7 . At the time, this was interpreted exclusively as a loss of active Na + resorption, because it was not widely recognized yet that the intestinal mucosa also secreted Cl − in an electrogenic fashion 8 …”

Functional characterization and localization of AQP3 in the human colon

“…It is generally accepted that these important fluid transfers are associated with salt reabsorption or secretion. Nevertheless, it is still a subject of controversy whether the absorptive processes are located in the surface (and villus) cells, if the secretory processes are located in the crypt cells (4,5) and if the transport-associated water movements are transcellular or paracellular (6,7).…”

TMEM16 proteins: the long awaited calcium-activated chloride channels?

“…Studies of transepithelial secretion of fluid and electrolytes in the intestine have historically led the way to our understanding of basic concepts of this important physiological process and its associated pathophysiology (18). It is well known that cAMP-mediated agonists, and Vibrio cholera toxin, are able to elicit CFTR-mediated chloride secretion.…”