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F1000Research 2019Vasoactive intestinal peptide (VIP), a gut peptide hormone originally reported as a vasodilator in 1970, has multiple physiological and pathological effects on... (Review)
Review
Vasoactive intestinal peptide (VIP), a gut peptide hormone originally reported as a vasodilator in 1970, has multiple physiological and pathological effects on development, growth, and the control of neuronal, epithelial, and endocrine cell functions that in turn regulate ion secretion, nutrient absorption, gut motility, glycemic control, carcinogenesis, immune responses, and circadian rhythms. Genetic ablation of this peptide and its receptors in mice also provides new insights into the contribution of VIP towards physiological signaling and the pathogenesis of related diseases. Here, we discuss the impact of VIP on gastrointestinal function and diseases based on recent findings, also providing insight into its possible therapeutic application to diabetes, autoimmune diseases and cancer.
Topics: Animals; Gastrointestinal Diseases; Gastrointestinal Tract; Mice; Receptors, Vasoactive Intestinal Peptide, Type II; Receptors, Vasoactive Intestinal Polypeptide, Type I; Signal Transduction; Vasoactive Intestinal Peptide
PubMed: 31559013
DOI: 10.12688/f1000research.18039.1 -
The Journal of Physiology Dec 2013Cerebrovascular reactivity is the change in cerebral blood flow in response to a vasodilatory or vasoconstrictive stimulus. Measuring variations of cerebrovascular... (Review)
Review
Cerebrovascular reactivity is the change in cerebral blood flow in response to a vasodilatory or vasoconstrictive stimulus. Measuring variations of cerebrovascular reactivity between different regions of the brain has the potential to not only advance understanding of how the cerebral vasculature controls the distribution of blood flow but also to detect cerebrovascular pathophysiology. While there are standardized and repeatable methods for estimating the changes in cerebral blood flow in response to a vasoactive stimulus, the same cannot be said for the stimulus itself. Indeed, the wide variety of vasoactive challenges currently employed in these studies impedes comparisons between them. This review therefore critically examines the vasoactive stimuli in current use for their ability to provide a standard repeatable challenge and for the practicality of their implementation. Such challenges include induced reductions in systemic blood pressure, and the administration of vasoactive substances such as acetazolamide and carbon dioxide. We conclude that many of the stimuli in current use do not provide a standard stimulus comparable between individuals and in the same individual over time. We suggest that carbon dioxide is the most suitable vasoactive stimulus. We describe recently developed computer-controlled MRI compatible gas delivery systems which are capable of administering reliable and repeatable vasoactive CO2 stimuli.
Topics: Brain; Cerebrovascular Circulation; Humans; Hypercapnia; Vasodilation
PubMed: 24081155
DOI: 10.1113/jphysiol.2013.259150 -
Blood Transfusion = Trasfusione Del... Oct 2017Here we review recent data and the evolving understanding of the role of red blood cell-derived microparticles (RMPs) in normal physiology and in disease progression.... (Review)
Review
Here we review recent data and the evolving understanding of the role of red blood cell-derived microparticles (RMPs) in normal physiology and in disease progression. Microparticles (MPs) are small membrane vesicles derived from various parent cell types. MPs are produced in response to a variety of stimuli through several cytoskeletal and membrane phospholipid changes. MPs have been investigated as potential biomarkers for multiple disease processes and are thought to have biological effects, most notably in: promotion of coagulation, production and handling of reactive oxygen species, immune modulation, angiogenesis, and in apoptosis. Specifically, RMPs are produced normally during RBC maturation and their production is accelerated during processing and storage for transfusion. Several factors during RBC storage are known to trigger RMP production, including: increased intracellular calcium, increased potassium leakage, and energy failure with ATP depletion. Of note, RMP composition differs from that of intact RBCs, and the nature and composition of RMP components are affected by both storage duration and the character of storage solutions. Recognised RMP bioactivities include: promotion of coagulation, immune modulation, and promotion of endothelial adhesion, as well as influence upon vasoregulation via nitric oxide (NO) scavenging. Of particular relevance, RMPs are more avid NO scavengers than intact RBCs and this feature has been proposed as a mechanism for the impaired oxygen delivery homeostasis that has been observed following transfusion. Preliminary human studies demonstrate that circulating RMP abundance increases with RBC transfusion and is associated with altered plasma vasoactivity and abnormal vasoregulation. In summary, RMPs are submicron particles released from stored RBCs, with demonstrated vasoactive properties that appear to disturb oxygen delivery homeostasis. The clinical impact of RMPs in transfusion recipients is an area of continued investigation.
Topics: Animals; Apoptosis; Biomarkers; Blood Coagulation; Blood Preservation; Blood Transfusion; Cell Communication; Cell-Derived Microparticles; Erythrocytes; Homeostasis; Humans; Inflammation; Nitric Oxide; Oxidative Stress; Oxygen; Vasodilation
PubMed: 28686154
DOI: 10.2450/2017.0353-16 -
British Journal of Pharmacology May 2012The vasoactive intestinal peptide receptor 1 (VPAC(1) ) belongs to family B of GPCRs and is activated upon binding of vasoactive intestinal peptide (VIP) and pituitary... (Review)
Review
The vasoactive intestinal peptide receptor 1 (VPAC(1) ) belongs to family B of GPCRs and is activated upon binding of vasoactive intestinal peptide (VIP) and pituitary AC-activating polypeptide neuropeptides. Widely distributed throughout body, VPAC(1) plays important regulatory roles in human physiology and physiopathology. Like most members of the GPCR-B family, VPAC(1) receptor is predicted to follow the actual paradigm of a common 'two-domain' model of natural ligand action. However the precise structural basis for ligand binding, receptor activation and signal transduction are still incompletely understood due in part to the absence of X-ray crystal structure of the whole receptor and to significant structural differences with the most extensively studied family of receptor, the GPCR-A/rhodopsin family. Here, we try to summarize the current knowledge of the molecular mechanisms involved in VPAC(1) receptor activation and signal transduction. This includes search for amino acids involved in the two-step process of VIP binding, in the stabilization of VPAC(1) inactive and active conformations, and in binding and activation of G proteins.
Topics: Amino Acid Sequence; Animals; Humans; Ligands; Neuropeptides; Pituitary Adenylate Cyclase-Activating Polypeptide; Protein Binding; Protein Conformation; Receptors, Vasoactive Intestinal Polypeptide, Type I; Signal Transduction; Vasoactive Intestinal Peptide
PubMed: 21806602
DOI: 10.1111/j.1476-5381.2011.01616.x -
The Journal of Headache and Pain Feb 2018In migraineurs pituitary adenylate cyclase activating peptide1-38 (PACAP1-38) is a potent migraine provoking substance and the accompanying long lasting flushing... (Review)
Review
BACKGROUND
In migraineurs pituitary adenylate cyclase activating peptide1-38 (PACAP1-38) is a potent migraine provoking substance and the accompanying long lasting flushing suggests degranulation of mast cells. Infusion of the closely related vasoactive intestinal peptide (VIP) either induces headache or flushing. This implicates the pituitary adenylate cyclase activating peptide type I receptor (PAC1) to be involved in the pathophysiology of PACAP1-38 provoked headaches. Here we review studies characterizing the effects of mainly PACAP but also of VIP on cerebral and meningeal arteries and mast cells.
DISCUSSION
PACAP1-38, PACAP1-27 and VIP dilate cerebral and meningeal arteries from several species including man. In rat cerebral and meningeal arteries the dilation seems to be mediated preferably via vasoactive intestinal peptide receptor type 1 (VPAC1) receptors while, in human, middle meningeal artery dilation induced via vasoactive intestinal peptide receptor type 2 (VPAC2) receptors cannot be ruled out. PACAP1-38 is a strong degranulator of peritoneal and dural mast cells while PACAP1-27 and VIP only have weak effects. More detailed characterization studies suggest that mast cell degranulation is not mediated via the known receptors for PACAP1-38 but rather via a still unknown receptor coupled to phospholipase C.
CONCLUSION
It is suggested that PACAP1-38 might induce migraine via degranulation of dural mast cells via a yet unknown receptor.
Topics: Animals; Cell Degranulation; Humans; Mast Cells; Meningeal Arteries; Migraine Disorders; Pituitary Adenylate Cyclase-Activating Polypeptide; Pituitary Gland; Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide; Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide, Type I; Receptors, Vasoactive Intestinal Peptide, Type II; Receptors, Vasoactive Intestinal Polypeptide, Type I; Signal Transduction; Vasoactive Intestinal Peptide
PubMed: 29460121
DOI: 10.1186/s10194-017-0822-2 -
Kidney360 Jan 2021
Topics: Arteriovenous Fistula; Arteriovenous Shunt, Surgical; Humans; Kidney Diseases; Renal Dialysis
PubMed: 35368825
DOI: 10.34067/KID.0006262020 -
International Journal of Molecular... Aug 2022Increased fructose consumption induces metabolic-syndrome-like pathologies and modulates vasoactivity and the participation of nitric oxide (NO) and hydrogen sulfide...
Vasoactive Effects of Chronic Treatment with Fructose and Slow-Releasing HS Donor GYY-4137 in Spontaneously Hypertensive Rats: The Role of Nitroso and Sulfide Signalization.
Increased fructose consumption induces metabolic-syndrome-like pathologies and modulates vasoactivity and the participation of nitric oxide (NO) and hydrogen sulfide (HS). We investigated whether a slow-releasing HS donor, GYY-4137, could exert beneficial activity in these conditions. We examined the effect of eight weeks of fructose intake on the blood pressure, biometric parameters, vasoactive responses, and NO and HS pathways in fructose-fed spontaneously hypertensive rats with or without three weeks of GYY-4137 i.p. application. GYY-4137 reduced triacylglycerol levels and blood pressure, but not adiposity, and all were increased by fructose intake. Fructose intake generally enhanced endothelium-dependent vasorelaxation, decreased adrenergic contraction, and increased protein expression of interleukin-6 (IL-6), tumor necrosis factor alpha (TNFα), and concentration of conjugated dienes in the left ventricle (LV). Although GYY-4137 administration did not affect vasorelaxant responses, it restored disturbed contractility, LV oxidative damage and decreased protein expression of TNFα in fructose-fed rats. While the participation of endogenous HS in vasoactive responses was not affected by fructose treatment, the expression of HS-producing enzyme cystathionine β-synthase in the LV was increased, and the stimulation of the NO signaling pathway improved endothelial function in the mesenteric artery. On the other hand, chronic treatment with GYY-4137 increased the expression of HS-producing enzyme cystathionine γ-lyase in the LV and stimulated the beneficial pro-relaxant and anti-contractile activity of endogenous HS in thoracic aorta. Our results suggest that sulfide and nitroso signaling pathways could trigger compensatory vasoactive responses in hypertensive rats with metabolic disorder. A slow HS-releasing donor could partially amend metabolic-related changes and trigger beneficial activity of endogenous HS.
Topics: Animals; Cystathionine gamma-Lyase; Fructose; Hydrogen Sulfide; Morpholines; Nitric Oxide; Organothiophosphorus Compounds; Rats; Rats, Inbred SHR; Sulfides; Tumor Necrosis Factor-alpha
PubMed: 36012477
DOI: 10.3390/ijms23169215 -
CNS & Neurological Disorders Drug... Nov 2010Vasoactive intestinal peptide (VIP) is a basic 28 amino acid peptide that binds to a member of the class II family of G protein-coupled receptors (GPCRs). It is widely... (Review)
Review
Vasoactive intestinal peptide (VIP) is a basic 28 amino acid peptide that binds to a member of the class II family of G protein-coupled receptors (GPCRs). It is widely expressed throughout the body and plays an important role in numerous biological functions. VIP acts via three different GPCRs: VPAC1, VPAC2, and PAC1, which have been identified in various tissues, including brain, lung, kidney, gastrointestinal tract, tongue, and also on immunocompetent cells such as macrophages and lymphocytes. There is mounting evidence that VIP expression and signaling is altered in numerous neurological disorders, and it is becoming apparent that VIP and its receptors could be therapeutic loci for the treatment of several pathological conditions of the central nervous system. In this review, we describe the pathology of several major neurological disorders and discuss the potential pharmacotherapeutic role of VIP and its receptors for the treatment of disorders such as Alzheimer's disease, Parkinson's disease, and Autism Spectrum Disorders.
Topics: Animals; Drug Delivery Systems; Humans; Models, Biological; Nervous System Diseases; Receptors, Vasoactive Intestinal Peptide; Vasoactive Intestinal Peptide
PubMed: 20632962
DOI: 10.2174/187152710793361595 -
Translational Stroke Research Feb 2023Therapeutic induction of collateral flow as a means to salvage tissue and improve outcome from acute ischemic stroke is a promising approach in the era in which... (Review)
Review
Therapeutic induction of collateral flow as a means to salvage tissue and improve outcome from acute ischemic stroke is a promising approach in the era in which endovascular therapy is no longer time-dependent but collateral-dependent. The importance of collateral flow enhancement as a therapeutic for acute ischemic stroke extends beyond those patients with large amounts of salvageable tissue. It also has the potential to extend the time window for reperfusion therapies in patients who are ineligible for endovascular thrombectomy. In addition, collateral enhancement may be an important adjuvant to neuroprotective agents by providing a more robust vascular route for which treatments can gain access to at risk tissue. However, our understanding of collateral hemodynamics, including under comorbid conditions that are highly prevalent in the stroke population, has hindered the efficacy of collateral flow augmentation for improving stroke outcome in the clinical setting. This review will discuss our current understanding of pial collateral function and hemodynamics, including vasoactivity that is critical for enhancing penumbral perfusion. In addition, mechanisms by which collateral flow can be increased during acute ischemic stroke to limit ischemic injury, that may be different depending on the state of the brain and vasculature prior to stroke, will also be reviewed.
Topics: Humans; Ischemic Stroke; Brain Ischemia; Stroke; Brain; Thrombectomy; Collateral Circulation; Cerebrovascular Circulation
PubMed: 35416577
DOI: 10.1007/s12975-022-01019-2 -
International Journal of Molecular... Jul 2022Pituitary Adenylate Cyclase-Activating Peptide (PACAP) and Vasoactive Intestinal Peptide (VIP) are neuropeptides involved in a diverse array of physiological and... (Review)
Review
Pituitary Adenylate Cyclase-Activating Peptide (PACAP) and Vasoactive Intestinal Peptide (VIP) are neuropeptides involved in a diverse array of physiological and pathological processes through activating the PACAP subfamily of class B1 G protein-coupled receptors (GPCRs): VIP receptor 1 (VPAC1R), VIP receptor 2 (VPAC2R), and PACAP type I receptor (PAC1R). VIP and PACAP share nearly 70% amino acid sequence identity, while their receptors PAC1R, VPAC1R, and VPAC2R share 60% homology in the transmembrane regions of the receptor. PACAP binds with high affinity to all three receptors, while VIP binds with high affinity to VPAC1R and VPAC2R, and has a thousand-fold lower affinity for PAC1R compared to PACAP. Due to the wide distribution of VIP and PACAP receptors in the body, potential therapeutic applications of drugs targeting these receptors, as well as expected undesired side effects, are numerous. Designing selective therapeutics targeting these receptors remains challenging due to their structural similarities. This review discusses recent discoveries on the molecular mechanisms involved in the selectivity and signaling of the PACAP subfamily of receptors, and future considerations for therapeutic targeting.
Topics: Amino Acid Sequence; Pituitary Adenylate Cyclase-Activating Polypeptide; Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide, Type I; Receptors, Vasoactive Intestinal Peptide, Type II; Receptors, Vasoactive Intestinal Polypeptide, Type I; Signal Transduction; Vasoactive Intestinal Peptide
PubMed: 35897648
DOI: 10.3390/ijms23158069