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Current Opinion in Endocrinology,... Feb 2016To summarize the roles of vasoactive intestinal peptide (VIP)/pituitary adenylate cyclase activating polypeptide (PACAP) and their receptors (VPAC1, VPAC2, PAC1) in... (Review)
Review
PURPOSE OF REVIEW
To summarize the roles of vasoactive intestinal peptide (VIP)/pituitary adenylate cyclase activating polypeptide (PACAP) and their receptors (VPAC1, VPAC2, PAC1) in human tumors as well as their role in potential novel treatments.
RECENT FINDINGS
Considerable progress has been made in understanding of the effects of VIP/PACAP on growth of various tumors as well as in the signaling cascades involved, especially in the role of transactivation of the epidermal growth factor family. The overexpression of VPAC1/2 and PAC1 on a number of common neoplasms (breast, lung, prostate, central nervous system and neuroblastoma) is receiving increased attention both as a means of tumor imaging the location and extent of these tumors, as well as for targeted directed treatment, by coupling cytotoxic agents to VIP/PACAP analogues.
SUMMARY
VIP/PACAP has prominent growth effects on a number of common neoplasms, which frequently overexpressed the three subtypes of their receptors. The increased understanding of their signaling cascades, effect on tumor growth/differentiation and the use of the overexpression of these receptors for localization/targeted cytotoxic delivery are all suggesting possible novel tumor treatments.
Topics: Humans; Neoplasms; 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; Vasoactive Intestinal Peptide
PubMed: 26702849
DOI: 10.1097/MED.0000000000000218 -
Birth Defects Research Aug 2020Amniotic band syndrome (ABS) includes limb deficiencies accompanied by fibrous strands originating from the amniotic lining. Terminal transverse limb deficiencies (TTLD)...
INTRODUCTION
Amniotic band syndrome (ABS) includes limb deficiencies accompanied by fibrous strands originating from the amniotic lining. Terminal transverse limb deficiencies (TTLD) appear to be similar but lack fibrous strands. Both are hypothesized to result from vascular disruption. For ABS, limb deficiencies are considered secondary to amnion rupture. We explored an alternative possibility-that TTLD is the primary defect and ABS is secondary.
METHODS
Using data from the National Birth Defects Prevention Study, we expanded on a previous study. We examined smoking, alcohol, and medications categorized by indicated vasoactivity as markers of vascular disruption. Logistic regression models with Firth's penalized likelihood were used to estimate adjusted odds ratios (aORs) and 95% confidence intervals (CIs).
RESULTS
Use of bronchodilators and aspirin appeared to increase the risk of ABS, while decongestants and nonaspirin NSAIDs increased the risk of TTLD. The risk of ABS was markedly increased in cases reporting combinations of vasoactive exposures, particularly alcohol and aspirin (aOR 3.7, 95% CI 1.6, 7.8), and alcohol and bronchodilators (aOR 3.4, 95% CI 1.4, 7.5). Increased risk of TTLD due to combinations of vasoactive exposures was only observed for smoking and decongestants (aOR 2.3, 95% CI 1.4, 3.6).
CONCLUSIONS
Exposures associated with increased risk of ABS had no apparent association with TTLD, supporting previous evidence that these may be distinct phenotypes. ABS appears to be associated with combined exposures with vasodilation properties, such as alcohol and bronchodilators, while increased risk of TTLD may be associated with smoking and decongestants, both vasoconstrictive exposures.
Topics: Amniotic Band Syndrome; Humans; Infant, Newborn; Odds Ratio; Smoking
PubMed: 32573119
DOI: 10.1002/bdr2.1740 -
The Journal of Headache and Pain Mar 2018Pituitary adenylate cyclase-activating peptide (PACAP) is a neuropeptide implicated in a wide range of functions, such as nociception and in primary headaches. Regarding... (Review)
Review
Pituitary adenylate cyclase-activating peptide (PACAP) is a neuropeptide implicated in a wide range of functions, such as nociception and in primary headaches. Regarding its localization, PACAP has been observed in the sensory trigeminal ganglion (TG), in the parasympathetic sphenopalatine (SPG) and otic ganglia (OTG), and in the brainstem trigeminocervical complex. Immunohistochemistry has shown PACAP-38 in numerous cell bodies of SPG/OTG, co-stored with vasoactive intestinal peptide (VIP), nitric oxide synthase (NOS) and, to a minor degree, with choline acetyltransferase. PACAP has in addition been found in a subpopulation of calcitonin gene-related peptide (CGRP)-immunoreactive cells in the trigeminal system. The PACAP/VIP receptors (PAC, VPAC, and VPAC) are present in sensory neurons and in vascular smooth muscle related to the trigeminovascular system. It is postulated that PACAP is involved in nociception. In support, abolishment of PACAP synthesis or reception leads to diminished pain responses, whereas systemic PACAP-38 infusion triggers pain behavior in animals and delayed migraine-like attacks in migraine patients without marked vasodilatory effects. In addition, increased plasma levels have been documented in acute migraine attacks and in cluster headache, in accordance with findings in experimental models of trigeminal activation. This suggest that the activation of the trigeminal system may result in elevated venous levels of PACAP, a change that can be reduced when headache is treated. The data presented in this review indicate that PACAP and its receptors may be promising targets for migraine therapeutics.
Topics: Animals; Ganglia, Parasympathetic; Headache Disorders, Primary; Humans; Neurons, Afferent; Pituitary Adenylate Cyclase-Activating Polypeptide; Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide; Receptors, Vasoactive Intestinal Polypeptide, Type I; Trigeminal Ganglion; Vasoactive Intestinal Peptide
PubMed: 29523978
DOI: 10.1186/s10194-018-0852-4 -
PloS One 2022Vasoactive treatment is a cornerstone in treating hypoperfusion in cardiogenic shock following acute myocardial infarction (AMICS). The purpose was to compare the...
BACKGROUND
Vasoactive treatment is a cornerstone in treating hypoperfusion in cardiogenic shock following acute myocardial infarction (AMICS). The purpose was to compare the achievement of treatment targets and outcome in relation to vasoactive strategy in AMICS patients stratified according to the Society of Cardiovascular Angiography and Interventions (SCAI) shock classification.
METHODS
Retrospective analysis of patients with AMICS admitted to cardiac intensive care unit at two tertiary cardiac centers during 2010-2017 with retrieval of real-time hemodynamic data and dosages of vasoactive drugs from intensive care unit databases.
RESULTS
Out of 1,249 AMICS patients classified into SCAI class C, D, and E, mortality increased for each shock stage from 34% to 60%, and 82% (p<0.001). Treatment targets of mean arterial blood pressure > 65mmHg and venous oxygen saturation > 55% were reached in the majority of patients; however, more patients in SCAI class D and E had values below treatment targets within 24 hours (p<0.001) despite higher vasoactive load and increased use of epinephrine for each severity stage (p<0.001). In univariate analysis no significant difference in mortality within SCAI class D and E regarding vasoactive strategy was observed, however in SCAI class C, epinephrine was associated with higher mortality and a significantly higher vasoactive load to reach treatment targets. In multivariate analysis there was no statistically association between individually vasoactive choice within each SCAI class and 30-day mortality.
CONCLUSION
Hemodynamic treatment targets were achieved in most patients at the expense of increased vasoactive load and more frequent use of epinephrine for each shock severity stage. Mortality was high regardless of vasoactive strategy; only in SCAI class C, epinephrine was associated with a significantly higher mortality, but the signal was not significant in adjusted analysis.
Topics: Angiography; Epinephrine; Humans; Myocardial Infarction; Retrospective Studies; Shock, Cardiogenic
PubMed: 35925990
DOI: 10.1371/journal.pone.0272279 -
Journal of Biomedical Science Aug 2016Vasoactive intestinal peptide (VIP) plays important roles in many biological functions, such as, stimulation of contractility in the heart, vasodilation, promoting... (Review)
Review
Vasoactive intestinal peptide (VIP) plays important roles in many biological functions, such as, stimulation of contractility in the heart, vasodilation, promoting neuroendocrine-immune communication, lowering arterial blood pressure, and anti-inflammatory and immune-modulatory activity. Osteoarthritis (OA) is a chronic and degenerative bone disease, which is one of the most common causes of disability and most common in both sexes as people become older. Interestingly VIP can prevent chronic cartilage damage and joint remodeling. This review article provides update information on the association of VIP and OA and its treatment. Evidences suggest that VIP is down-regulated in synovial fluid of OA, and VIP down-regulation leads to increase in the production of pro-inflammatory cytokines that might contribute to the pathogenesis of OA; however contradictory reports also exist suggesting that accumulation of VIP in joints can also contribute OA. A number of studies indicated that up-regulation of VIP can counteract the action of pro-inflammatory stimuli and alleviate the pain in OA. More clinical investigations are necessary to determine the biology of VIP and its therapeutic potential in OA that might represent the future standards of care for OA.
Topics: Cytokines; Down-Regulation; Humans; Osteoarthritis; Synovial Fluid; Up-Regulation; Vasoactive Intestinal Peptide
PubMed: 27553659
DOI: 10.1186/s12929-016-0280-1 -
Frontiers in Endocrinology 2022Owing to the increasing prevalence of type 2 diabetes, the development of novel hypoglycemic drugs has become a research hotspot, with the ultimate goal of developing... (Review)
Review
Owing to the increasing prevalence of type 2 diabetes, the development of novel hypoglycemic drugs has become a research hotspot, with the ultimate goal of developing therapeutic drugs that stimulate glucose-induced insulin secretion without inducing hypoglycemia. Vasoactive intestinal peptide (VIP), a 28-amino-acid peptide, can stimulate glucose-dependent insulin secretion, particularly by binding to VPAC2 receptors. VIP also promotes islet β-cell proliferation through the forkhead box M1 pathway, but the specific molecular mechanism remains to be studied. The clinical application of VIP is limited because of its short half-life and wide distribution in the human body. Based on the binding properties of VIP and VPAC2 receptors, VPAC2-selective agonists have been developed to serve as novel hypoglycemic drugs. This review summarizes the physiological significance of VIP in glucose homeostasis and the potential therapeutic value of VPAC2-selective agonists in type 2 diabetes.
Topics: Diabetes Mellitus, Type 2; Glucose; Humans; Hypoglycemic Agents; Insulin Secretion; Receptors, Vasoactive Intestinal Peptide, Type II; Vasoactive Intestinal Peptide
PubMed: 36204104
DOI: 10.3389/fendo.2022.984198 -
Pediatric Critical Care Medicine : a... Dec 2022To determine whether there are clinically relevant and reproducible Vasoactive Inotrope Score (VIS) trajectories in children with shock during the acute phase of... (Observational Study)
Observational Study
OBJECTIVES
To determine whether there are clinically relevant and reproducible Vasoactive Inotrope Score (VIS) trajectories in children with shock during the acute phase of critical illness.
DESIGN
Retrospective, observational cohort study.
SETTING
Two tertiary, academic PICUs.
PATIENTS
Children (< 18 yr old) who required vasoactive infusions within 24 hours of admission to the PICU. Those admitted post cardiac surgery were excluded.
INTERVENTIONS
None.
MEASUREMENTS AND MAIN RESULTS
An hourly VIS was calculated for the first 72 hours after initiation of vasoactives. Group-based trajectory modeling (GBTM) was applied to a derivation set (75% of encounters) and compared with the trajectories in a validation set (25% of encounters) using the same variables. The primary outcome was in-hospital mortality, and the secondary outcome was multiple organ dysfunction syndrome (MODS) on day 7. A total of 1,828 patients met inclusion criteria, and 309 (16.9%) died. GBTM identified four subgroups that were reproducible in the validation set: "Mild, fast resolving shock" ( n = 853 [47%]; mortality 9%), "Moderate, slow resolving shock" ( n = 422 [23%]; mortality 15%), "Moderate, prolonged shock" ( n = 312 [17%]; mortality 21%), and "Severe, prolonged shock" ( n = 241 [13%]; mortality 40%). There was a significant difference in mortality, MODS on day 7, and suspected infection ( p < 0.001) across groups. The "Mild, fast resolving shock" and "Severe, prolonged shock" groups were identifiable within the first 24 hours. The "Moderate, slow resolving" and "Moderate, prolonged shock" groups were indistinguishable in the first 24 hours after initiation of vasoactives but differed in in-hospital mortality and MODS on day 7. Hydrocortisone administration was independently associated with poor outcomes in the "Mild, fast resolving shock" group.
CONCLUSIONS
We uncovered four distinct and reproducible VIS trajectory groups that were associated with different risk factors, response to therapy, and outcomes in children with shock. Characterizing VIS trajectory groups in the acute phase of critical illness may enable better prognostication and more targeted management.
Topics: Child; Humans; Multiple Organ Failure; Critical Illness; Retrospective Studies; Hospital Mortality; Cohort Studies; Intensive Care Units, Pediatric
PubMed: 36053068
DOI: 10.1097/PCC.0000000000003070 -
Annals of Palliative Medicine Mar 2021Vasoactive intestinal peptide (VIP) is an important neurotransmitter involved in the modulation of gastrointestinal function through the stimulation of VIP receptors....
BACKGROUND
Vasoactive intestinal peptide (VIP) is an important neurotransmitter involved in the modulation of gastrointestinal function through the stimulation of VIP receptors. However, the expression of VPAC1R, VPAC2R and PAC1R in the human Lower esophageal sphincter (LES) has not been fully clarified. Therefore, the purpose of this study is to explore the expression of these receptors in the human Lower esophageal sphincter, the responses of the Lower esophageal sphincter to Vasoactive intestinal peptide, and the role of Vasoactive intestinal peptide receptors in the responses.
METHODS
Sling and clasp fiber samples of LES were acquired from patients undergoing subtotal esophagectomy, while circular muscle bundles from the esophagus and gastric fundus were used as control groups. Western blotting and RT-PCR technology were performed to determine the expression of the three VIP receptor subtypes. The isometric tension responses of the muscle sample strips to Ro25-1553 and PG99-465, and the effect of electrical field stimulation (EFS) on the sling and clasp fibers were studied.
RESULTS
We found that VPAC2R messenger RNA (mRNA) and protein were expressed in the sling and clasp fibers of human LES. However, no VPAC1R or PAC1R mRNA and protein expressions were found in the LES samples. The sling and clasp fibers of the LES produced significant concentration-dependent relaxation following exposure to Ro25-1553 and EFS could induce them to produce frequency-dependent relaxation. Furthermore, the relaxation responses of the LES were inhibited by PG99-465 and induced by EFS and Ro25-1553.
CONCLUSIONS
VPAC2R, but not VPAC1R or PAC1R, is expressed by the human LES. The relaxation responses of the LES generated by the VIP receptor agonist Ro25-1553 and EFS could be inhibited by the selective VPAC2 receptor antagonist PG99-465. VPAC2R may be important for the generation of relaxation and functional regulation of the LES.
Topics: Electric Stimulation; Esophageal Sphincter, Lower; Esophagectomy; Humans; Neurotransmitter Agents; Receptors, Vasoactive Intestinal Peptide
PubMed: 33849096
DOI: 10.21037/apm-21-193 -
Expert Opinion on Drug Metabolism &... Jul 2015Drug-induced vascular injury (DIVI) is a serious problem in preclinical studies of vasoactive molecules and for survivors of pediatric cancers. DIVI is often observed in...
Drug-induced vascular injury (DIVI) is a serious problem in preclinical studies of vasoactive molecules and for survivors of pediatric cancers. DIVI is often observed in rodents and some larger animals, primarily with drugs affecting vascular tone, but not in humans; however, DIVI observed in animal studies often precludes a drug candidate from continuing along the development pipeline. Thus, there is great interest by the pharmaceutical industry to identify quantifiable human biomarkers of DIVI. Small-scale endothelialized tissue-engineered blood vessels using human cells represent a promising approach to screen drug candidates and develop alternatives to cancer therapeutics in vitro. We identify several technical challenges that remain to be addressed, including high-throughput systems to screen large numbers of candidates, identification of suitable cell sources and establishing and maintaining a differentiated state of the vessel wall cells. Adequately addressing these challenges should yield novel platforms to screen drugs and develop new therapeutics to treat cardiovascular disease.
Topics: Animals; Biomarkers; Blood Vessel Prosthesis; Blood Vessels; Drug Design; Drug Evaluation, Preclinical; High-Throughput Screening Assays; Humans; Species Specificity; Tissue Engineering; Toxicity Tests; Vascular Diseases
PubMed: 26028128
DOI: 10.1517/17425255.2015.1047342 -
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