Stimulatory effect of pituitary adenylate cyclase-activating polypeptide 6-38, M65 and vasoactive intestinal polypeptide 6-28 on trigeminal sensory neurons

Neuroscience
É SághyÉ Szőke

Abstract

Pituitary adenylate cyclase-activating polypeptide (PACAP) acts on G protein-coupled receptors: the specific PAC1 and VPAC1/VPAC2 receptors. PACAP6-38 was described as a potent PAC1/VPAC2 antagonist in several models, but recent studies reported its agonistic behaviors proposing novel receptorial mechanisms. Since PACAP in migraine is an important research tool, we investigated the effect of PACAP and its peptide fragments on trigeminal primary sensory neurons. Effect of the peptides was studied with ratiometric Ca-imaging technique using the fluorescent indicator fura-2 AM on primary cultures of rat and mouse trigeminal ganglia (TRGs) neurons. Specificity testing was performed on PAC1, VPAC1 and VPAC2 receptor-expressing cell lines with both fluorescent and radioactive Ca-uptake methods. Slowly increasing intracellular free calcium concentration [Ca(2+)]i was detected after PACAP1-38, PACAP1-27, vasoactive intestinal polypeptide (VIP) and the selective PAC1 receptor agonist maxadilan administration on TRG neurons, but interestingly, PACAP6-38, VIP6-28 and the PAC1 receptor antagonist M65 also caused similar activation. The VPAC2 receptor agonist BAY 55-9837 induced similar activation, while the VPAC1 receptor agonist Ala(11,22...Continue Reading

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Citations

Dec 14, 2016·The Journal of Headache and Pain·Elena BacchelliLuigi Alberto Pini
Oct 5, 2017·British Journal of Pharmacology·Tahlia Sundrum, Christopher S Walker
Mar 11, 2018·The Journal of Headache and Pain·Lars EdvinssonLászló Vécsei
Feb 21, 2018·The Journal of Headache and Pain·Inger Jansen-Olesen, Sara Hougaard Pedersen
Mar 2, 2018·Nature Reviews. Disease Primers·Arne MayShuu-Jiun Wang
Jan 25, 2018·The Journal of Pharmacology and Experimental Therapeutics·Ichiro TakasakiTakashi Kurihara
Feb 22, 2018·Neurotherapeutics : the Journal of the American Society for Experimental NeuroTherapeutics·Anne Luise Haulund VollesenMessoud Ashina
Aug 9, 2018·The Journal of Headache and Pain·Eloisa Rubio-BeltránUNKNOWN European Headache Federation School of Advanced Studies (EHF-SAS)

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