Vasoactive intestinal peptide

Vasoactive intestinal peptide also known as the vasoactive intestinal polypeptide or VIP is a peptide hormone containing 29 amino acid residues that is produced in many tissues of vertebrates including the gut, pancreas and suprachiasmatic nuclei of the hypothalamus in the brain. In humans, the vasoactive intestinal peptide is encoded by the VIP gene. VIP has a half-life (t) in the blood of about two minutes. Function 1. With respect to the digestive system, VIP seems to induce smooth muscle relaxation (lower esophageal sphincter, stomach, gallbladder), stimulate secretion of water into pancreatic juice and bile, and cause inhibition of gastric acid secretion and absorption from the intestinal lumen. Its role in the intestine is to greatly stimulate secretion of water and electrolytes, as well as stimulating contraction of enteric smooth muscle, dilating peripheral blood vessels, stimulating pancreatic bicarbonate secretion, and inhibiting gastrin-stimulated gastric acid secretion. These effects work together to increase motility. 2. It also has the function of stimulating pepsinogen secretion by chief cells. 3. It is also found in the brain and some autonomic nerves. One region of the brain includes a specific area of the suprachiasmatic nuclei (SCN), the location of the 'master circadian pacemaker'. The SCN coordinates daily timekeeping in the body and VIP plays a key role in communication between individual brain cells within this region. Further, VIP is also involved in synchronising the timing of SCN function with the environmental lightdark cycle. Combined, these roles in the SCN make VIP a crucial component of the mammalian circadian timekeeping machinery. 4. VIP helps to regulate prolactin secretion 5. It is also found in the heart and has significant effects on the cardiovascular system. It causes coronary vasodilation as well as having a positive inotropic and chronotropic effect. Research is being performed to see if it may have a beneficial role in the treatment of heart failure. 6. VIP provokes vaginal lubrication in normal women, doubling the total volume of lubrication produced in one study. 7. GH-RH is a member of the VIP family and stimulates Growth Hormone secretion in the anterior pituitary gland. 8. VIP has potent vascular and airway dilatory actions, potent anti-inflammatory actions, improving blood circulation to the heart and lung, and modulation of airway secretions. Vasoactive intestinal peptide receptor

There are two known receptors for the vasoactive intestinal peptide (VIP) termed VPAC1 and VPAC2. These receptors bind both VIP and pituitary adenylate cyclase-activating polypeptide (PACAP) to some degree. Both receptors are members of the 7 transmembrane G protein-coupled receptor family. VPAC1 is distributed widely in the CNS, liver, lung, intestine and T-lymphocytes. VPAC2 is found in the CNS, pancreas, skeletal muscle, heart, kidney, adipose tissue, testis, and stomach. Pathology VIP is overproduced in VIPoma. Can be associated with Multiple Endocrine Neoplasia Type 1 (Pituitary, parathyroid and pancreatic tumors). Symptoms are typically:Profuse nonbloody/non-mucoid diarrhea (3L+) causing dehydration and the associated electrolyte disturbances such as hypokalemia and contraction metabolic alkalosis. VIP also implicated in cancer. Clinical significance VIP has emerged as a promising drug candidate for the treatment of several diseases. A number of clinical applications of VIP or its derivatives have been developed; however, VIPbased drugs are not yet in clinical use, possibly because of mainly two serious problems: (1) poor metabolic stability and (2) poor penetration to the desired site of action. Activation of VPAC2R, but not VPAC1R, reduced the loss of skeletal muscle mass and force during conditions of skeletal muscle atrophy resulting from corticosteroid administration, denervation, casting-induced disuse, increased skeletal muscle mass, and force of nonatrophying muscles. Helodermin, and helospectin are selective for the human VIP2 receptor subtypes.VPAC2R agonists may have utility for the treatment of skeletal musclewasting diseases. VIP analogues are being evaluated for treatment of heart failure. They enhance Ca mediated intracardiac neuroexcitability. Vasoactive intestinal peptide (VIP) is widely expressed throughout the cardiopulmonary system and exerts a variety of biological actions, including potent vascular and airway dilatory actions, potent anti-inflammatory actions, improving blood circulation to the heart and lung, and modulation of airway secretions.The development of long-acting VIP analogues, in combination with appropriate drug delivery systems, may provide clinically useful agents for the treatment of PAH, asthma, and COPD.