Vasoactive intestinal peptide (VIP) is a peptide composed of 28 amino acids that acts as both a hormone and a neurotransmitter. Its name provides clues to its initial discovery and a primary characteristic. “Vasoactive” indicates its ability to influence the diameter of blood vessels, while “intestinal” refers to the gut, where it was first isolated. Despite its name, VIP is not confined to the intestines and is found in many tissues, including the pancreas and various parts of the central and peripheral nervous systems.
Primary Functions in the Body
In the gastrointestinal (GI) system, VIP plays a role in regulating digestive processes. One of its actions is the relaxation of smooth muscles in the walls of the stomach, gallbladder, and intestines, which helps modulate gut motility. VIP also stimulates the secretion of water, electrolytes, and bicarbonate from the pancreas into the intestinal lumen. This process aids in neutralizing stomach acid, and it also inhibits the secretion of gastric acid.
The cardiovascular system is influenced by VIP, primarily through its ability to widen blood vessels, a process known as vasodilation. It acts on the smooth muscle cells of blood vessel walls, causing them to relax. This widening of the vessels increases blood flow and decreases blood pressure. In the heart, VIP-containing nerve fibers are found near structures that control heart rate, and the peptide can increase the force of heart contractions.
Within the nervous system, VIP functions as a neurotransmitter, sending signals between nerve cells. It is widely distributed in both the central nervous system (the brain and spinal cord) and the peripheral nervous system. A specific role occurs in the suprachiasmatic nucleus (SCN) of the hypothalamus, the body’s master clock. VIP is important for synchronizing the daily rhythms of neurons within the SCN, which helps regulate the body’s circadian rhythms.
The respiratory system also responds to the presence of VIP. In the airways, VIP acts as a bronchodilator, relaxing the smooth muscles that line the bronchial tubes. This action widens the airways, making breathing easier. Nerves containing VIP are found in the human lung around the smooth muscle and airway glands, where its release can counteract forces that cause bronchoconstriction.
VIP and Medical Conditions
An excess of vasoactive intestinal peptide can lead to a rare medical condition, most commonly caused by a VIPoma. This is a type of neuroendocrine tumor that secretes large, uncontrolled amounts of VIP, with about 90% originating in the pancreas. The quantities of VIP released by the tumor cause a set of symptoms known as Verner-Morrison syndrome, or WDHA syndrome.
WDHA syndrome is an acronym that describes its primary features: Watery Diarrhea, Hypokalemia, and Achlorhydria. The watery diarrhea is the most prominent symptom and is often severe and persists even when the patient is fasting. Hypokalemia refers to dangerously low levels of potassium in the blood, a result of losing large quantities in the diarrheal fluid. Achlorhydria is a condition characterized by the absence of stomach acid. This combination of symptoms can lead to severe dehydration, muscle weakness, and metabolic imbalances.
While conditions related to excess VIP are more clearly defined, states of VIP deficiency are less understood and are an area of ongoing investigation. Research suggests potential associations between low VIP levels and certain health issues. For example, because VIP is a vasodilator, a deficiency might contribute to some forms of hypertension. Its role in nerve signaling has also led to research into its potential connection with conditions like erectile dysfunction.
Therapeutic and Diagnostic Applications
One of the primary uses of vasoactive intestinal peptide is diagnostic. Measuring the concentration of VIP in a patient’s blood is a way to investigate the cause of certain symptoms. A blood test showing elevated levels of VIP is an indicator for diagnosing a VIPoma, especially in patients with severe, watery diarrhea. The test is performed by taking a blood sample while a patient is symptomatic, as the tumor may release VIP intermittently.
VIP and drugs designed to mimic its actions, known as analogs, hold therapeutic potential. Researchers are exploring its use in treating pulmonary arterial hypertension, a type of high blood pressure affecting the arteries in the lungs. Inhaled forms of the peptide have been shown to decrease pressure in the pulmonary artery and improve exercise capacity in patients.
Its function as a bronchodilator has also made it a candidate for treating respiratory diseases. Studies have investigated inhaled VIP as a potential therapy for conditions like asthma and chronic obstructive pulmonary disease (COPD). The development of more stable and selective synthetic analogs is a focus of this research, aiming to harness the beneficial effects of VIP while minimizing potential side effects.