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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(11,22,28)VIP had no significant effect on [Ca(2+)]i. It was proven that the Ca(2+)-influx originated from intracellular stores using radioactive calcium-45 uptake experiment and Ca-free solution. On the specific receptor-expressing cell lines the antagonists inhibited the stimulating actions of the respective agonists, but had no effects by themselves. PACAP6-38, M65 and VIP6-28, which were described as antagonists in numerous studies in several model systems, act as agonists on TRG primary sensory neurons. Currently unknown receptors or splice variants linked to distinct signal transduction pathways might explain these differences.

Titel:	Stimulatory effect of pituitary adenylate cyclase-activating polypeptide 6-38, M65 and vasoactive intestinal polypeptide 6-28 on trigeminal sensory neurons.
Autor/in / Beteiligte Person:	Sághy, É ; Payrits, M ; Helyes, Z ; Reglődi, D ; Bánki, E ; Tóth, G ; Couvineau, A ; Szőke, É
Link:	Zum Volltext
Zeitschrift:	Neuroscience, Jg. 308 (2015-11-12), S. 144
Veröffentlichung:	[New York?] : Elsevier Science ; <i>Original Publication</i>: Oxford, Elmsford, N. Y., Pergamon Press, 2015
Medientyp:	academicJournal
ISSN:	1873-7544 (electronic)
DOI:	10.1016/j.neuroscience.2015.08.043
Schlagwort:	Animals CHO Cells Calcium metabolism Cells, Cultured Cricetulus Humans Mice Rats, Wistar Receptors, Vasoactive Intestinal Peptide, Type II antagonists & inhibitors Receptors, Vasoactive Intestinal Peptide, Type II metabolism Receptors, Vasoactive Intestinal Polypeptide, Type I agonists Receptors, Vasoactive Intestinal Polypeptide, Type I metabolism Sensory Receptor Cells physiology TRPV Cation Channels metabolism Trigeminal Ganglion physiology Voltage-Sensitive Dye Imaging Insect Proteins pharmacology Peptide Fragments pharmacology Pituitary Adenylate Cyclase-Activating Polypeptide pharmacology Sensory Receptor Cells drug effects Sensory System Agents pharmacology Trigeminal Ganglion drug effects Vasoactive Intestinal Peptide pharmacology
Sonstiges:	Nachgewiesen in: MEDLINE Sprachen: English Publication Type: Journal Article; Research Support, Non-U.S. Gov't Language: English [Neuroscience] 2015 Nov 12; Vol. 308, pp. 144-56. <i>Date of Electronic Publication: </i>2015 Aug 28. MeSH Terms: Insect Proteins / pharmacology ; Peptide Fragments / pharmacology ; Pituitary Adenylate Cyclase-Activating Polypeptide / pharmacology ; Sensory Receptor Cells / drug effects ; Sensory System Agents / pharmacology ; Trigeminal Ganglion / drug effects ; Vasoactive Intestinal Peptide / *pharmacology ; Animals ; CHO Cells ; Calcium / metabolism ; Cells, Cultured ; Cricetulus ; Humans ; Mice ; Rats, Wistar ; Receptors, Vasoactive Intestinal Peptide, Type II / antagonists & inhibitors ; Receptors, Vasoactive Intestinal Peptide, Type II / metabolism ; Receptors, Vasoactive Intestinal Polypeptide, Type I / agonists ; Receptors, Vasoactive Intestinal Polypeptide, Type I / metabolism ; Sensory Receptor Cells / physiology ; TRPV Cation Channels / metabolism ; Trigeminal Ganglion / physiology ; Voltage-Sensitive Dye Imaging Contributed Indexing: Keywords: G protein-coupled receptor; PAC1; PACAP6-38; VPAC1; VPAC2; trigeminal ganglia Substance Nomenclature: 0 (Insect Proteins) ; 0 (Peptide Fragments) ; 0 (Pituitary Adenylate Cyclase-Activating Polypeptide) ; 0 (Receptors, Vasoactive Intestinal Peptide, Type II) ; 0 (Receptors, Vasoactive Intestinal Polypeptide, Type I) ; 0 (Sensory System Agents) ; 0 (TRPV Cation Channels) ; 0 (maxadilan protein, Lutzomyia longipalpis) ; 0 (pituitary adenylate-cyclase-activating-peptide (6-38)) ; 0 (vasoactive intestinal peptide (1-7)-GRF (8-27), Lys(15)-Arg(16)-Leu(27)-) ; 0 (vasoactive intestinal peptide (6-28)) ; 37221-79-7 (Vasoactive Intestinal Peptide) ; SY7Q814VUP (Calcium) Entry Date(s): Date Created: 20150901 Date Completed: 20160719 Latest Revision: 20151010 Update Code: 20231215

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