ArticleThe Journal of clinical investigation2004
The pituitary adenylate cyclase-activating polypeptide is a physiological inhibitor of platelet activation.
Article in The Journal of clinical investigation, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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The trial behind it
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Who cites it
24 citing papers in PubMed, 59 citations in OpenAlex.
- Platelet Membrane Receptors and Signalling Pathways.Handbook of experimental pharmacology · 2026Review
- Exploring the Role of Neuropeptide PACAP in Cytoskeletal Function Using Spectroscopic Methods.International journal of molecular sciences · 2024Article
- PACAP Induces Light Aversion in Mice by an Inheritable Mechanism Independent of CGRP.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2021Article
- Macrophage Polarization and Alveolar Bone Healing Outcome: Despite a Significant M2 Polarizing Effect, VIP and PACAP Treatments Present a Minor Impact in Alveolar Bone Healing in Homeostatic Conditions.Frontiers in immunology · 2021Article
- Discovery of PACAP and its receptors in the brain.The journal of headache and pain · 2018Review
- β-Arrestin1 and 2 differentially regulate PACAP-induced PAC1 receptor signaling and trafficking.PloS one · 2018Article
- Pituitary adenylate cyclase-activating polypeptide (PACAP) in zebrafish models of nephrotic syndrome.PloS one · 2017Article
- Platelet abnormalities in nephrotic syndrome.Pediatric nephrology (Berlin, Germany) · 2016Review
- Ring chromosome 18 in combination with 18q12.1 (DTNA) interstitial microdeletion in a patient with multiple congenital defects.Molecular cytogenetics · 2016Article
- PACAP enhances axon outgrowth in cultured hippocampal neurons to a comparable extent as BDNF.PloS one · 2015Article
- Screening for intellectual disability using high-resolution CMA technology in a retrospective cohort from Central Brazil.PloS one · 2014Article
- Increased behavioral and neuronal responses to a hallucinogenic drug in PACAP heterozygous mutant mice.PloS one · 2014Article
- A non-syndromic intellectual disability associated with a de novo microdeletion at 7q and 18p, microduplication at Xp, and 18q partial trisomy detected using chromosomal microarray analysis approach.Molecular cytogenetics · 2014Article
- Platelet defects in congenital variant of Rett syndrome patients with FOXG1 mutations or reduced expression due to a position effect at 14q12.European journal of human genetics : EJHG · 2013Article
- Platelets of mice heterozygous for neurobeachin, a candidate gene for autism spectrum disorder, display protein changes related to aberrant protein kinase A activity.Molecular autism · 2013Article
- Pituitary adenylate cyclase-activating polypeptide prevents contrast-induced nephropathy in a novel mouse model.Physiological reports · 2013Article
- Article
- Pituitary Adenylate Cyclase-Activating Polypeptide (PACAP) impairs the regulation of apoptosis in megakaryocytes by activating NF-κB: a proteomic study.Molecular & cellular proteomics : MCP · 2012Article
- Effect of VPAC1 Blockade on Adipose Tissue Formation and Composition in Mouse Models of Nutritionally Induced Obesity.Journal of obesity · 2010Article
- The role of vasoactive intestinal peptide (VIP) in megakaryocyte proliferation.Journal of molecular neuroscience : MN · 2009Article
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The pituitary adenylate cyclase-activating polypeptide (PACAP) is a neuropeptide of the vasoactive intestinal peptide/secretin/glucagon superfamily. Studies in two related patients with a partial trisomy 18p revealed three copies of the PACAP gene and elevated PACAP concentrations in plasma. The patients suffer from severe mental retardation and have a bleeding tendency with mild thrombocytopenia, and their fibroblasts show increased PACAP mRNA levels. The PACAP receptor (vasoactive intestinal peptide/pituitary adenylate cyclase-activating peptide receptor 1 [VPAC1]) in platelets and fibroblasts is coupled to adenylyl cyclase activation. Accordingly, we found increased basal cAMP levels in patients' platelets and fibroblasts, providing a basis for the reduced platelet aggregation in these patients. Megakaryocyte-specific transgenic overexpression of PACAP in mice correspondingly increased PACAP release from platelets, reduced platelet activation, and prolonged the tail bleeding time. In contrast, the PACAP antagonist PACAP(6-38) or a monoclonal PACAP antibody enhanced the collagen-induced aggregation of normal human platelets, and in PACAP knockout mice, an increased platelet sensitivity toward collagen was found. Thus, we found that PACAP modulates platelet function and demonstrated what we believe to be the first hemostatic defect associated with PACAP overexpression; our study suggests the therapeutic potential to manage arterial thrombosis or bleeding by administration of PACAP mimetics or inhibitors, respectively.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.