{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T13:19:38Z","timestamp":1790169578997,"version":"4.1.0"},"reference-count":86,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2022,2,14]],"date-time":"2022-02-14T00:00:00Z","timestamp":1644796800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Brain Research Program","award":["2017-1.2.1-NKP-2017-00002 (NAP-2; Chronic Pain Research Group)"],"award-info":[{"award-number":["2017-1.2.1-NKP-2017-00002 (NAP-2; Chronic Pain Research Group)"]}]},{"name":"Economy Development and Innovation Operative Programme","award":["(GINOP)-2.3.2-15-2016-00050 (Peptidergic Signaling in Health and Disease; PEPSYS)"],"award-info":[{"award-number":["(GINOP)-2.3.2-15-2016-00050 (Peptidergic Signaling in Health and Disease; PEPSYS)"]}]},{"name":"Economy Development and Innovation Operative Programme","award":["GINOP 2.3.2-15-2016-0034"],"award-info":[{"award-number":["GINOP 2.3.2-15-2016-0034"]}]},{"name":"Economy Development and Innovation Operative Programme","award":["GINOP-2.3.4-15-2020-00010"],"award-info":[{"award-number":["GINOP-2.3.4-15-2020-00010"]}]},{"name":"Economy Development and Innovation Operative Programme","award":["GINOP-2.3.1-20-2020-00001"],"award-info":[{"award-number":["GINOP-2.3.1-20-2020-00001"]}]},{"name":"Human Resource Operative Programme","award":["(EFOP) 3.6.2-16-2017-00008 (2017-2019)"],"award-info":[{"award-number":["(EFOP) 3.6.2-16-2017-00008 (2017-2019)"]}]},{"name":"Human Resource Operative Programme","award":["EFOP-3.6.1-16-2016-00004"],"award-info":[{"award-number":["EFOP-3.6.1-16-2016-00004"]}]},{"DOI":"10.13039\/501100011019","name":"National Research Development and Innovation Office","doi-asserted-by":"publisher","award":["OTKA FK132587"],"award-info":[{"award-number":["OTKA FK132587"]}],"id":[{"id":"10.13039\/501100011019","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Educating Experts of the Future: Developing Bioinformatics and Biostatistics competencies of European Biomedical Students","award":["BECOMING, 2019-1-HU01-KA203-061251"],"award-info":[{"award-number":["BECOMING, 2019-1-HU01-KA203-061251"]}]},{"name":"National Research, Development and Innovation Fund of Hungary","award":["TKP2020-IKA-08"],"award-info":[{"award-number":["TKP2020-IKA-08"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Pituitary adenylate cyclase-activating polypeptide (PACAP) is a broadly expressed neuropeptide which has diverse effects in both the peripheral and central nervous systems. While its neuroprotective effects have been shown in a variety of disease models, both animal and human data support the role of PACAP in migraine generation. Both PACAP and its truncated derivative PACAP(6-38) increased calcium influx in rat trigeminal ganglia (TG) primary sensory neurons in most experimental settings. PACAP(6-38), however, has been described as an antagonist for PACAP type I (known as PAC1), and Vasoactive Intestinal Polypeptide Receptor 2 (also known as VPAC2) receptors. Here, we aimed to compare the signaling pathways induced by the two peptides using transcriptomic analysis. Rat trigeminal ganglion cell cultures were incubated with 1 \u00b5M PACAP-38 or PACAP(6-38). Six hours later RNA was isolated, next-generation RNA sequencing was performed and transcriptomic changes were analyzed to identify differentially expressed genes. Functional analysis was performed for gene annotation using the Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Reactome databases. We found 200 common differentially expressed (DE) genes for these two neuropeptides. Both PACAP-38 and PACAP(6-38) treatments caused significant downregulation of NADH: ubiquinone oxidoreductase subunit B6 and upregulation of transient receptor potential cation channel, subfamily M, member 8. The common signaling pathways induced by both peptides indicate that they act on the same target, suggesting that PACAP activates trigeminal primary sensory neurons via a mechanism independent of the identified and cloned PAC1\/VPAC2 receptor, either via another target structure or a different splice variant of PAC1\/VPAC2 receptors. Identification of the target could help to understand key mechanisms of migraine.<\/jats:p>","DOI":"10.3390\/ijms23042120","type":"journal-article","created":{"date-parts":[[2022,2,14]],"date-time":"2022-02-14T20:26:42Z","timestamp":1644870402000},"page":"2120","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["PACAP-38 Induces Transcriptomic Changes in Rat Trigeminal Ganglion Cells Related to Neuroinflammation and Altered Mitochondrial Function Presumably via PAC1\/VPAC2 Receptor-Independent Mechanism"],"prefix":"10.3390","volume":"23","author":[{"given":"Krisztina","family":"Tak\u00e1cs-Lov\u00e1sz","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Pharmacotherapy, Medical School & Szent\u00e1gothai Research Centre, Molecular Pharmacology Research Group, Centre for Neuroscience, University of P\u00e9cs, H-7624 P\u00e9cs, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00f3zsef","family":"Kun","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Pharmacotherapy, Medical School & Szent\u00e1gothai Research Centre, Molecular Pharmacology Research Group, Centre for Neuroscience, University of P\u00e9cs, H-7624 P\u00e9cs, Hungary"},{"name":"Szent\u00e1gothai Research Centre, Bioinformatics Research Group, Genomics and Bioinformatics Core Facility, University of P\u00e9cs, H-7624 P\u00e9cs, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timea","family":"Acz\u00e9l","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Pharmacotherapy, Medical School & Szent\u00e1gothai Research Centre, Molecular Pharmacology Research Group, Centre for Neuroscience, University of P\u00e9cs, H-7624 P\u00e9cs, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4043-3428","authenticated-orcid":false,"given":"P\u00e9ter","family":"Urb\u00e1n","sequence":"additional","affiliation":[{"name":"Szent\u00e1gothai Research Centre, Bioinformatics Research Group, Genomics and Bioinformatics Core Facility, University of P\u00e9cs, H-7624 P\u00e9cs, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Attila","family":"Gyenesei","sequence":"additional","affiliation":[{"name":"Szent\u00e1gothai Research Centre, Bioinformatics Research Group, Genomics and Bioinformatics Core Facility, University of P\u00e9cs, H-7624 P\u00e9cs, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kata","family":"B\u00f6lcskei","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Pharmacotherapy, Medical School & Szent\u00e1gothai Research Centre, Molecular Pharmacology Research Group, Centre for Neuroscience, University of P\u00e9cs, H-7624 P\u00e9cs, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u00c9va","family":"Sz\u0151ke","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Pharmacotherapy, Medical School & Szent\u00e1gothai Research Centre, Molecular Pharmacology Research Group, Centre for Neuroscience, University of P\u00e9cs, H-7624 P\u00e9cs, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zsuzsanna","family":"Helyes","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Pharmacotherapy, Medical School & Szent\u00e1gothai Research Centre, Molecular Pharmacology Research Group, Centre for Neuroscience, University of P\u00e9cs, H-7624 P\u00e9cs, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,2,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2861","DOI":"10.2174\/1381612043383548","article-title":"Pituitary Adenylate Cyclase Activating Polypeptide: A Potential Neuroprotective Peptide","volume":"10","year":"2004","journal-title":"Curr. 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