Vasoactive intestinal peptide (VIP) is present in the peripheral and the central nervous systems where it functions as a nonadrenergic, noncholinergic neurotransmitter or neuromodulator. Significant concentrations of VIP are present in the gastrointestinal tract, heart, lungs, thyroid, kidney, urinary bladder, genital organs and the brain. On a molar basis, VIP is 50-100 times more potent than acetylcholine as a vasodilator. VIP release in the body is stimulated by high frequency (10-20 Hz) nerve stimulation and by cholinergic agonists, serotonin, dopaminergic agonists, prostaglandins (PGE, PGD), and nerve growth factor. The VIP peptide combines with its receptor and dose-dependently activates adenylyl cyclase. The vasodilatory effect of VIP in different vascular tissues or species also may be due to increases in nitric oxide, cyclic GMP, and other signaling agents. In the heart, VIP immunoreactive nerve fibers are present not only in the epicardial coronary arteries and veins, but also the sinoatrial node, atrium, interatrial septum, atrioventricular node, intracardiac ganglia, and ventricles (right ventricle >> left ventricle). In the coronary arterial walls, VIP may contribute to the regulation of normal coronary vasomotor tone. In research animals and in humans, VIP, administered into the coronary artery or intravenously, increases the epicardial coronary artery cross-sectional area, decreases coronary vascular resistance, and significantly increases coronary artery blood flow. High frequency parasympathetic (vagal) nerve stimulation also releases endogenous VIP in the coronary vessels and heart and significantly increases coronary artery blood flow. In addition, the release of VIP in the heart is increased during coronary artery occlusion and during reperfusion where VIP may promote local blood flow and may have a free-radical scavenging effect. VIP also has a primary positive inotropic effect on cardiac muscle that is enhanced by its ability to facilitate ventricular-vascular coupling by reducing mean arterial pressure by 10-15%. In concentrations of 10(-8)-10(-5) mol, VIP augments developed isometric force and increases atrial and ventricular contractility. The presence of VIP-immunoreactive nerve fibers in and around the sinus and the atrioventricular nodes of mammals strongly suggests that this peptide can affect the heart rate. In this regard, endogenously released or exogenous VIP can significantly increase the heart rate and has a more potent effect on heart rate than does norepinephrine. The presence and significant cardiovascular effects of VIP in the heart suggests that this peptide is important in the regulation of coronary blood flow, cardiac contraction, and heart rate. Current investigations are defining the physiological role of VIP in the regulation of cardiovascular function.

Vasoactive intestinal peptide: cardiovascular effects.

Cell proliferation, the balance between mitosis and apoptosis is the result of the continuous integration of a number of different signal transduction pathways stimulated in a cell at any given point in its life. Neuroblastoma cells regulate the switch between mitosis and death, according both to intrinsic factors and extrinsic factors, such as growth factor withdrawal and action of the vitamin A derivative, retinoic acid. In this review, we describe the balance of some factors regulating growth and death of human neuroblastoma cells in vitro. These dynamic studies are necessarily performed on cell lines, which offer controlled conditions enabling the disection of the complex stimuli mediating survival and growth (IGF, trk, BDNF) and death (transglutaminase, free radicals, Bcl-2). Although the conclusions drawn may therefore not be directly applicable to tumour cells in vivo, the results herein discussed are of sufficient significance to warrant in vivo relevance.

Retinoids and the control of growth/death decisions in human neuroblastoma cell lines

Vasoactive intestinal polypeptide as mediator of asthma.

Vasoactive intestinal polypeptide (VIP), a neuropeptide with wide distribution in the central and peripheral nervous systems, has a broad spectrum of biologic actions. Usually acting as a neurotransmitter or neuromodulator but sometimes also as a blood-borne hormone, it participates in the regulation of a variety of major body functions and may be an important factor in the pathogenesis of several diseases.

Vasoactive intestinal polypeptide biologic role in health and disease

Stearyl-Nle-17-VIP (SNV) is a novel agonist of vasoactive intestinal peptide (VIP) exhibiting a 100-fold greater potency than the parent molecule and specificity for a receptor associated with neuronal survival. Here, mice deficient in apolipoprotein E (ApoE), a molecule associated with the etiology of Alzheimer's disease, served as a model to investigate the developmental and protective effects of SNV. In comparison to control animals, the deficient mice exhibited (a) reduced amounts of VIP messenger RNA; (b) decreased cholinergic activity (c) significant retardation in the acquisition of developmental milestones: forelimb placing behavior and cliff avoidance behavior; and (d) learning and memory impairments. Daily injections of SNV to ApoE-deficient newborn pups resulted in increased cholinergic activity and marked improvements in the time of acquisition of behavioral milestones, with peptide-treated animals developing as fast as control animals and exhibiting improved cognitive functions after cessation of peptide treatment. Specificity was demonstrated in that treatment with a related peptide (PACAP), pituitary adenylate cyclase-activating peptide, produced only limited amelioration. As certain genotypes of ApoE increase the probability of Alzheimer's disease, early counseling and preventive treatments may now offer an important route for therapeutics design. © 1997 John Wiley & Sons, Inc. J Neurobiol 33: 329–342, 1997

Protection against developmental retardation in apolipoprotein E-deficient mice by a fatty neuropeptide: Implications for early treatment of Alzheimer's disease

Vasoactive intestinal peptide (VIP) is a major neuropeptide involved in multiple functions such as vasodilation, smooth-muscle relaxation, sweat secretion, gastrointestinal peristalsis, pancreatic function, and brain activity. In view of the multiple roles associated with VIP,it is important to understand its gene regulation. We have recently isolated the human VIPgene and determined its structure. By in situ hybridization techniques we have now localized this gene to the long arm of chromosome 6, 6q24, a chromosomal region that has been shown previously to contain the coding sequences for the nuclear protooncogene c-myb.Genes found in close proximity to each other on the chromosome are often functionally related and, as VIPis primarily expressed in the nervous system, we investigated the possible correlation of c-mybto VIPin neuronal tissue. A sharp peak of c-mybmRNA was observed in the hippocampus of 3-day-old rats, preceding the peak of VIPmRNA that occurs in this brain area at 8 days of age. Thus, the protooncogene c-mybmay be associated with events in brain development occurring prior to the appearance of elevated concentrations of VIP.

Sequential expression in the nervous system of c-myb and VIP genes, located in human chromosomal region 6q24.

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Sequential expression in the nervous system of c-myb and VIP genes, located in human chromosomal region 6q24.