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Annals of the New York Academy of... Nov 2019Neuropeptides function as neuromodulators in the brain, whereby they are released in a paracrine manner and activate G protein-coupled receptors (GPCRs) in adjacent... (Review)
Review
Neuropeptides function as neuromodulators in the brain, whereby they are released in a paracrine manner and activate G protein-coupled receptors (GPCRs) in adjacent cells. Because neuropeptides are made in, and secreted from, cancer cells, then bind to cell surface receptors, they function in an autocrine manner. Bombesin (BB)-like peptides synthesized by neuroendocrine tumor small cell lung cancer (SCLC) bind to BB receptors (BBRs), causing phosphatidylinositol turnover and phosphorylation of extracellular signal-regulated kinase (ERK). Phosphorylated ERK enters the nucleus and alters gene expression of SCLC cells, stimulating growth. Vasoactive intestinal peptide (VIP) addition to SCLC cells increases their release rate of BB-like peptides via activation of VIP receptors (VIPR), leading to activation of adenylyl cyclase and subsequent elevation of cAMP. Protein kinase A is then stimulated, leading to phosphorylation of cyclic AMP response element binding protein (CREB), which alters gene expression and stimulates proliferation. The growth of SCLC is inhibited by BBR and VIPR antagonists. This review will focus on how GPCRs for VIP and BB are molecular targets for early detection and treatment of cancer.
Topics: Animals; Humans; Neoplasms; Phosphorylation; Receptors, Peptide
PubMed: 31074514
DOI: 10.1111/nyas.14100 -
Frontiers in Endocrinology 2020
Topics: Humans; Angiotensin-Converting Enzyme 2; Arthritis, Rheumatoid; Autoimmune Diseases; Drug Combinations; Gastrointestinal Neoplasms; Inflammation; Inflammatory Bowel Diseases; Neurodegenerative Diseases; Phentolamine; Receptors, G-Protein-Coupled; Vasoactive Intestinal Peptide
PubMed: 33101216
DOI: 10.3389/fendo.2020.588157 -
Cellular and Molecular Gastroenterology... 2024Although chronic diarrhea and constipation are common, the treatment is symptomatic because their pathophysiology is poorly understood. Accumulating evidence suggests...
BACKGROUND & AIMS
Although chronic diarrhea and constipation are common, the treatment is symptomatic because their pathophysiology is poorly understood. Accumulating evidence suggests that the microbiota modulates gut function, but the underlying mechanisms are unknown. We therefore investigated the pathways by which microbiota modulates gastrointestinal motility in different sections of the alimentary tract.
METHODS
Gastric emptying, intestinal transit, muscle contractility, acetylcholine release, gene expression, and vasoactive intestinal polypeptide (VIP) immunoreactivity were assessed in wild-type and Myd88Trif mice in germ-free, gnotobiotic, and specific pathogen-free conditions. Effects of transient colonization and antimicrobials as well as immune cell blockade were investigated. VIP levels were assessed in human full-thickness biopsies by Western blot.
RESULTS
Germ-free mice had similar gastric emptying but slower intestinal transit compared with specific pathogen-free mice or mice monocolonized with Lactobacillus rhamnosus or Escherichia coli, the latter having stronger effects. Although muscle contractility was unaffected, its neural control was modulated by microbiota by up-regulating jejunal VIP, which co-localized with and controlled cholinergic nerve function. This process was responsive to changes in the microbial composition and load and mediated through toll-like receptor signaling, with enteric glia cells playing a key role. Jejunal VIP was lower in patients with chronic intestinal pseudo-obstruction compared with control subjects.
CONCLUSIONS
Microbial control of gastrointestinal motility is both region- and bacteria-specific; it reacts to environmental changes and is mediated by innate immunity-neural system interactions. By regulating cholinergic nerves, small intestinal VIP plays a key role in this process, thus providing a new therapeutic target for patients with motility disorders.
Topics: Humans; Mice; Animals; Vasoactive Intestinal Peptide; Gastrointestinal Motility; Neuroglia; Cholinergic Agents
PubMed: 38061549
DOI: 10.1016/j.jcmgh.2023.11.012 -
Frontiers in Cellular and Infection... 2022Detection and transduction of environmental signals, constitute a prerequisite for successful parasite invasion; i.e., transmission, survival, pathogenesis and disease... (Review)
Review
Detection and transduction of environmental signals, constitute a prerequisite for successful parasite invasion; i.e., transmission, survival, pathogenesis and disease manifestation and dissemination, with diverse molecules functioning as inter-cellular signaling ligands. Receptors [i.e., G protein-coupled receptors (GPCRs)] and their associated transduction mechanisms, well conserved through evolution, specialize in this function. However, canonical GPCR-related signal transduction systems have not been described in , although orthologs, with reduced domains and function, have been identified in Trypanosomatidae. These inter-cellular communication means seem to be essential for multicellular and unicellular organism's survival. GPCRs are flexible in their molecular architecture and may interact with the so-called receptor activity-modifying proteins (RAMPs), which modulate their function, changing GPCRs pharmacology, acting as chaperones and regulating signaling and/or trafficking in a receptor-dependent manner. In the skin, vasoactive- and neuro- peptides released in response to the noxious stimuli represented by the insect bite may trigger parasite physiological responses, for example, chemotaxis. For instance, in (.) , sensory [Substance P, SP, chemoattractant] and autonomic [Vasoactive Intestinal Peptide, VIP, and Neuropeptide Y, NPY, chemorepellent] neuropeptides at physiological levels stimulate effects on parasite taxis. VIP and NPY chemotactic effects are impaired by their corresponding receptor antagonists, suggesting that the stimulated responses might be mediated by putative GPCRs (with essential conserved receptor domains); the effect of SP is blocked by [(D-Pro 2, D-Trp7,9]-Substance P (10 M)] suggesting that it might be mediated by neurokinin-1 transmembrane receptors. Additionally, vasoactive molecules like Calcitonin Gene-Related Peptide [CGRP] and Adrenomedullin [AM], exert a chemorepellent effect and increase the expression of a 24 kDa band recognized in western blot analysis by (human-)-RAMP-2 antibodies. search oriented towards GPCRs-like receptors and signaling cascades detected a RAMP-2-aligned sequence corresponding to folylpolyglutamate synthase and a RAMP-3 aligned protein, a hypothetical protein with yet unknown function, suggesting that in , CGRP and AM activities may be modulated by RAMP- (-2) and (-3) homologs. The possible presence of proteins and molecules potentially involved in GPCRs cascades, i.e., RAMPs, signpost conservation of ancient signaling systems associated with responses, fundamental for cell survival, (i.e., taxis and migration) and may constitute an open field for description of pharmacophores against parasites.
Topics: Calcitonin Gene-Related Peptide; Cell Communication; Humans; Leishmania; Receptor Activity-Modifying Proteins; Receptors, G-Protein-Coupled; Substance P
PubMed: 35651757
DOI: 10.3389/fcimb.2022.812848 -
Environmental Science and Pollution... Feb 2022Vasoactive intestinal peptide (VIP) is a neuropeptide that is produced by the lymphoid cells and plays a major role in immunological functions for controlling the... (Review)
Review
Vasoactive intestinal peptide (VIP) is a neuropeptide that is produced by the lymphoid cells and plays a major role in immunological functions for controlling the homeostasis of the immune system. VIP has been identified as a potent anti-inflammatory factor, in boosting both innate and adaptive immunity. Since December 2019, SARS-Cov-2 was found responsible for the disease COVID-19 which has spread worldwide. No specific therapies or 100% effective vaccines are yet available for the treatment of COVID-19. Drug repositioning may offer a strategy and several drugs have been repurposed, including lopinavir/ritonavir, remdesivir, favipiravir, and tocilizumab. This paper describes the main pharmacological properties of synthetic VIP drug (Aviptadil) which is now under clinical trials. A patented formulation of vasoactive intestinal polypeptide (VIP), named RLF-100 (Aviptadil), was developed and finally got approved for human trials by FDA in 2001 and in European medicines agency in 2005. It was awarded Orphan Drug Designation in 2001 by the US FDA for the treatment of acute respiratory distress syndrome and for the treatment of pulmonary arterial hypertension in 2005. Investigational new drug (IND) licenses for human trials of Aviptadil was guaranteed by both the US FDA and EMEA. Preliminary clinical trials seem to support Aviptadil's benefit. However, such drugs like Aviptadil in COVID-19 patients have peculiar safety profiles. Thus, adequate clinical trials are necessary for these compounds.
Topics: COVID-19; Drug Combinations; Humans; Phentolamine; SARS-CoV-2; Vasoactive Intestinal Peptide
PubMed: 34846667
DOI: 10.1007/s11356-021-17824-5 -
World Journal of Gastrointestinal... Apr 2022Vasoactive intestinal peptide (VIP) secreting tumour (VIPoma) is a rare functional neuroendocrine tumour that typically arises from pancreatic islet cells. These present... (Review)
Review
Vasoactive intestinal peptide (VIP) secreting tumour (VIPoma) is a rare functional neuroendocrine tumour that typically arises from pancreatic islet cells. These present as sporadic, solitary pancreatic neoplasias with an estimated incidence of one in ten million individuals per year. Only around 5% of VIPomas are associated with multiple endocrine neoplasia type I syndrome. Excessive VIP secretion produces a clinical syndrome characterized by refractory watery diarrhoea, hypokalemia and metabolic acidosis. These coupled with elevated plasma levels of VIP are diagnostic. The majority of VIPomas are malignant and have already metastasized at the time of diagnosis (60%). Metastases occur most frequently in the liver, or regional lymph nodes, lungs, kidneys and bones. Some reports of skin metastases have been documented. Complete surgical resection continues to be the only potentially curative treatment. However, when the neoplasia cannot be excised completely, surgical debulking may provide palliative benefit. Other palliative options have included recently the peptide receptor radionuclide therapy which has shown to be effective and well-tolerated. This article will review all aspects of pancreatic VIPomas highlighting aspects such as clinical presentation, diagnosis and management.
PubMed: 35582098
DOI: 10.4251/wjgo.v14.i4.808 -
Frontiers in Physiology 2019Healthy red blood cells (RBCs) deform readily in response to shear stress in the circulation, facilitating their efficient passage through capillaries. RBCs also export... (Review)
Review
Healthy red blood cells (RBCs) deform readily in response to shear stress in the circulation, facilitating their efficient passage through capillaries. RBCs also export vasoactive mediators in response to deformation and other physiological and pathological stimuli. Deoxygenation of RBC hemoglobin leads to the export of vasodilator and antiadhesive S-nitrosothiols (SNOs) and adenosine triphosphate (ATP) in parallel with oxygen transport in the respiratory cycle. Together, these mediated responses to shear stress and oxygen offloading promote the efficient flow of blood cells and in turn optimize oxygen delivery. In diseases including sickle cell anemia and conditions including conventional blood banking, these adaptive functions may be compromised as a result, for example, of limited RBC deformability, impaired mediator formation, or dysfunctional mediator export. Ongoing work, including single cell approaches, is examining relevant mechanisms and remedies in health and disease.
PubMed: 31803068
DOI: 10.3389/fphys.2019.01417 -
International Journal of Molecular... Jan 2023In this review, we discuss sympathetic regulation in normal and diabetic wound healing. Experimental denervation studies have confirmed that sympathetic nerve endings in... (Review)
Review
In this review, we discuss sympathetic regulation in normal and diabetic wound healing. Experimental denervation studies have confirmed that sympathetic nerve endings in skin have an important and complex role in wound healing. Vasoconstrictor neurons secrete norepinephrine (NE) and neuropeptide Y (NPY). Both mediators decrease blood flow and interact with inflammatory cells and keratinocytes. NE acts in an ambiguous way depending on receptor type. Beta2-adrenoceptors could be activated near sympathetic endings; they suppress inflammation and re-epithelialization. Alpha1- and alpha2-adrenoceptors induce inflammation and activate keratinocytes. Sudomotor neurons secrete acetylcholine (ACh) and vasoactive intestinal peptide (VIP). Both induce vasodilatation, angiogenesis, inflammation, keratinocytes proliferation and migration. In healthy skin, all effects are important for successful healing. In treatment of diabetic ulcers, mediator balance could be shifted in different ways. Beta2-adrenoceptors blockade and nicotinic ACh receptors activation are the most promising directions in treatment of diabetic ulcers with neuropathy, but they require further research.
Topics: Humans; Diabetes Complications; Diabetes Mellitus; Hemodynamics; Inflammation; Receptors, Adrenergic; Wound Healing; Sympathetic Nervous System; Neurons; Vasoconstriction; Skin; Skin Ulcer; Neuropeptide Y; Norepinephrine; Acetylcholine; Vasoactive Intestinal Peptide
PubMed: 36768369
DOI: 10.3390/ijms24032045 -
Acta Anaesthesiologica Scandinavica Aug 2022According to current guidelines, initial burn resuscitation should be performed with fluids alone. The aims of the study were to review the frequency of use of... (Review)
Review
BACKGROUND
According to current guidelines, initial burn resuscitation should be performed with fluids alone. The aims of the study were to review the frequency of use of vasoactive and/or inotropic drugs in initial burn resuscitation, and assess the benefits and harms of adding such drugs to fluids.
METHODS
A systematic literature search was conducted in PubMed, Embase, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, UpToDate, and SveMed+ through 3 December 2021. The search included studies on critically ill burn patients receiving vasoactive and/or inotropic drugs in addition to fluids within 48 h after burn injury.
RESULTS
The literature search identified 1058 unique publications that were screened for inclusion. After assessing 115 publications in full text, only two retrospective cohort studies were included. One study found that 16 out of 52 (31%) patients received vasopressor(s). Factors associated with vasopressor use were increasing age, burn depth, and % total body surface area (TBSA) burnt. Another study observed that 20 out of 111 (18%) patients received vasopressor(s). Vasopressor use was associated with increasing age, Baux score, and %TBSA burnt in addition to more frequent dialysis treatment and increased mortality. Study quality assessed by the Newcastle-Ottawa quality assessment scale was considered good in one study, but uncertain due to limited description of methods in the other.
CONCLUSION
This systematic review revealed that there is a lack of evidence regarding the benefits and harms of using vasoactive and/or inotropic drugs in addition to fluids during early resuscitation of patients with major burns.
Topics: Humans; Burns; Fluid Therapy; Resuscitation; Retrospective Studies
PubMed: 35583993
DOI: 10.1111/aas.14095 -
Nature Communications Jul 2023Peripheral sensory organ damage leads to compensatory cortical plasticity that is associated with a remarkable recovery of cortical responses to sound. The precise...
Peripheral sensory organ damage leads to compensatory cortical plasticity that is associated with a remarkable recovery of cortical responses to sound. The precise mechanisms that explain how this plasticity is implemented and distributed over a diverse collection of excitatory and inhibitory cortical neurons remain unknown. After noise trauma and persistent peripheral deficits, we found recovered sound-evoked activity in mouse A1 excitatory principal neurons (PNs), parvalbumin- and vasoactive intestinal peptide-expressing neurons (PVs and VIPs), but reduced activity in somatostatin-expressing neurons (SOMs). This cell-type-specific recovery was also associated with cell-type-specific intrinsic plasticity. These findings, along with our computational modelling results, are consistent with the notion that PV plasticity contributes to PN stability, SOM plasticity allows for increased PN and PV activity, and VIP plasticity enables PN and PV recovery by inhibiting SOMs.
Topics: Mice; Animals; Auditory Cortex; Interneurons; Neurons; Vasoactive Intestinal Peptide; Sound; Parvalbumins
PubMed: 37443148
DOI: 10.1038/s41467-023-39732-7