How VIP May Regulate Bowel Functions

What is Vasoactive Intestinal Polypeptide (VIP)?

Vasoactive Intestinal Polypeptide (VIP) belongs to a class of peptides called the neuropeptides. Neuropeptides are short sequence peptide chains produced by neurons that play a role as chemical messengers in various biochemical pathways.

The Vasoactive Intestinal Polypeptide is a potent vasodilator. It is also a neuromodulator and a neurotransmitter. It mainly functions in the gastrointestinal tract (GIT). Here, it modulates the smooth muscle activity mainly by relaxation and regulates epithelial cell secretion and blood flow to the GIT. It interacts with other gut chemicals to optimize gut function.
Researchers think it acts in a paracrine manner, being released from nerve terminals and acting locally on the receptors specific to it.

The VIP receptor belongs to the class of G-protein coupled receptors.

Protective Action of Vasoactive Intestinal Polypeptide Against Colitis

The intestinal epithelial wall is constantly exposed to extremely harsh conditions due to the passage of partially digested food, bile, and other acids. Maintaining the ace of the intestinal epithelial wall’s integrity is essential in protecting the small bowel from various immune-modulated inflammatory disorders- the most prominent is the inflammatory bowel disease or IBD (also known as colitis). Extensive research has shown that the enteric nervous system (ENS) includes the fibers of Vasoactive Intestinal Polypeptide-secreting nerves running through the lamina propria of the small intestine- plays an important and poorly understood role in the protection of the intestinal epithelium.

Research suggests that the disruption of the ENS during the pathogenesis of IBD plays a contributory role in the manifestation of the overt symptoms of IBD, including abdominal cramping and runny stool.
Several notable studies have pointed out a strong association between the significant decrease in the expression of Vasoactive Intestinal Polypeptide and VPA1C, its receptor, and IBD. This process concludes that VIP plays a vital protective role against inflammatory bowel disorders like IBD by maintaining the integrity and homeostasis of the intestinal epithelial wall.

Improvement of Bile Acid Secretion by Vasoactive Intestinal Polypeptide

Studies suggest that Vasoactive Intestinal Polypeptide causes an increase in bile acid secretion by the liver by enhancing the flow of bile and bile salt production. In studies conducted on duct-ligated rats, researchers noticed that the administration of exogenous VIP produced a significant increase in bile pH, bicarbonate concentration, and overall bile output in a dose-dependent manner.

Vasoactive Intestinal Polypeptide causes a significant stimulation of the cholangiocytes in the liver. This causes an increase in fluid and bicarbonate secretion via a potent cAMP-independent pathway.

The enhancement of bile secretion and output has been proven by a study conducted on 11 patients. Results showed that the exogenous administration of VIP in these patients resulted in a massive increase in bile volume of up to 60%.

Mechanism Involved in Improved Bile Secretion by VIP

As a potent vasodilator, Vasoactive Intestinal Polypeptide exerts a similar effect on the pancreatic vascular beds. Vasodilating the vessels that supply the pancreatic bed improves pancreatic secretory activity and enhances bile secretion.
Therefore, Vasoactive Intestinal Polypeptide plays a hemodynamic role due to its potency as a vasodilator and plays a protective and secretory role in the gut.

Improved Goblet Cell Growth by VIP

Goblet cells are a specialized type of mucosal cells in the intestinal epithelium that are the prime sites for mucosal absorption and digestion. Goblet cells are extensively present in large airways and the intestinal and colonic epithelium. In all these sites, it primarily functions to secrete mucously. Goblet cells produce the macro glycoprotein called mucin, the main component of mucous.

In the gut, goblet cells secrete a thick mucous coating that maintains intestinal epithelial homeostasis upon stimulation, either by exocytosis or acetylcholine. Therefore, goblet cells have a somewhat protective function. It has been studied that goblet cells serve as antigen importers and regulate the innate immune system.

Research on the Vasoactive Intestinal Polypeptide has shown that the exogenous administration of Vasoactive Intestinal Polypeptide resulted in a significant increase in the ileal concentrations of goblet cells in mice models aiding in the protection of the gut.

Gallbladder Relaxation via Vasoactive Intestinal Polypeptide (VIP)

Immunohistochemistry analysis of the gallbladder revealed VIP-secreting nerve fibers in its wall. The control of gallbladder contraction and relaxation is somewhat neurohumoral. It has been studied that Vasoactive Intestinal Polypeptide secretion results in a relaxation of the Sphincter of Oddi that permits and improves bile outflow.

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