Secretin

The small intestine is periodically assaulted by a flood of acid from the stomach, and it is important to put out that fire in a hurry to avoid acid burns. Secretin functions as a type of fireman: it is released in response to acid in the small intestine, and stimulates the pancreas and bile ducts to release a flood of bicarbonate base, which neutralizes the acid. Secretin is also of some historical interest, as it was the first hormone to be discovered.

Structure of Secretin and Its Receptors

Secretin is synthesized as a preprohormone, then proteolytically processed to yield a single 27-amino acid peptide by removal of the signal peptide plus amino and carboxy-terminal extensions. The sequence of the mature peptide is related to that of glucagon, vasoactive intestinal peptide and gastric inhibitory peptide.

The secretin receptor has seven membrane-spanning domains and characteristics typical of a G protein-coupled receptor.

Control and Physiologic Effects of Secretin

Secretin is secreted in response to one known stimulus: acidification of the duodenum, which occurs most commonly when liquified ingesta from the stomach are released into the small intestine.

The principal target for secretin is the pancreas, which responds by secreting a bicarbonate-rich fluid, which flows into the first part of the intestine through the pancreatic duct. Bicarbonate ion is a base and serves to neutralize the acid, thus preventing acid burns and establishing a pH conducive to the action of other digestive enzymes. A similar, but quantitatively less important response to secretin is elicited by bile duct cells, resulting in additional bicarbonate being dumped into the small gut.

As acid is neutralized by bicarbonate, the intestinal pH rises toward neutrality, and secretion of secretin is turned off.

Disease States

Secretin is sometimes used to treat peptic ulcers and for diagnosis of exocrine pancreatic disorders. Diseases associated with excessive or deficient secretion of secretin are not recognized.

In the late 1990's, manuscripts were published based on non-controlled case reports suggesting that intravenous therapy with secretin was a useful treatment for autism spectrum disorder. As with other purported treatments for autism, these reports generated a great deal of interest from parents of autistic children and autism support groups. In response to these pressures, numerous placebo-controlled clinical trials were conducted to evaluate secretin therapy for autism and not a single trial found a benefit of secretin therapy on behavior, language, or other signs of autism compared to children receiving placebo treatment. Secretin therapy for autism is considered ineffective.

Updated April 2019. Send comments to Richard.Bowen@colostate.edu