PMID- 30336190 OWN - NLM STAT- MEDLINE DCOM- 20190307 LR - 20190307 IS - 1873-7544 (Electronic) IS - 0306-4522 (Linking) VI - 393 DP - 2018 Nov 21 TI - Expression of Pituitary Adenylate Cyclase-activating Peptide, Calcitonin Gene-related Peptide and Headache Targets in the Trigeminal Ganglia of Rats and Humans. PG - 319-332 LID - S0306-4522(18)30665-1 [pii] LID - 10.1016/j.neuroscience.2018.10.004 [doi] AB - Neurotransmitter and headache target localization in the trigeminal ganglia (TG) might increase the understanding of sites of action, and mechanisms related to headache therapy. The overall aim of the study was to investigate the presence of migraine targets in the TG with particular emphasis on pituitary adenylate cyclase-activating peptide (PACAP) and calcitonin gene-related peptide (CGRP), known to be involved in cranial pain processing, and selected headache targets. Rat- and human TG were processed for immunohistochemistry. PACAP-38, CGRP and the headache targets were expressed in rat and human TG. PACAP receptors were confined to neurons and satellite glial cells (SGCs), however with variability between the receptor subtypes PACAP type I receptor (PAC(1)) and vasoactive intestinal peptide/PACAP receptors 1/2 (VPAC(1/2)). 5-Hydroxytryptamine (5-HT) receptors were expressed in neuronal somas in rat and human TG (human TG frequency: 5-HT(1D) > 5-HT(1B/1F)). Synaptosomal-associated protein 25 kDa (SNAP25) was primarily expressed in SGCs in humans, and neurons in rats, while synaptic vesicle glycoprotein 2A (SV2-A) was confined to SGCs and some neurons in rats and humans. Occasionally, PACAP-38-positive cells also expressed VPAC(1), SNAP25 and SV2-A. VPAC(1) was generally detected in SGCs enveloping PACAP-38-positive and -negative neuronal somas. Our study revealed potential sites of actions for anti-headache drugs such as PACAP receptor antagonists, Lasmiditan (5-HT(1F) agonist) and Botox (blocks exocytosis through SV2-A/SNAP25) in rat and human TG and considerable overlap between species in expression to specific cell types, except for VPAC(1) and SNAP25. CI - Copyright (c) 2018 IBRO. Published by Elsevier Ltd. All rights reserved. FAU - Frederiksen, Simona Denise AU - Frederiksen SD AD - Department of Clinical Experimental Research, Glostrup Research Institute, Rigshospitalet Glostrup, 2600 Glostrup, Denmark; Division of Experimental Vascular Research, Department of Clinical Sciences, Lund University, 221 84 Lund, Sweden. Electronic address: simona.frederiksen@hotmail.com. FAU - Warfvinge, Karin AU - Warfvinge K AD - Department of Clinical Experimental Research, Glostrup Research Institute, Rigshospitalet Glostrup, 2600 Glostrup, Denmark; Division of Experimental Vascular Research, Department of Clinical Sciences, Lund University, 221 84 Lund, Sweden. Electronic address: karin.warfvinge@med.lu.se. FAU - Ohlsson, Lena AU - Ohlsson L AD - Division of Experimental Vascular Research, Department of Clinical Sciences, Lund University, 221 84 Lund, Sweden. Electronic address: lena.ohlsson@med.lu.se. FAU - Edvinsson, Lars AU - Edvinsson L AD - Department of Clinical Experimental Research, Glostrup Research Institute, Rigshospitalet Glostrup, 2600 Glostrup, Denmark; Division of Experimental Vascular Research, Department of Clinical Sciences, Lund University, 221 84 Lund, Sweden. Electronic address: lars.edvinsson@med.lu.se. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20181015 PL - United States TA - Neuroscience JT - Neuroscience JID - 7605074 RN - 0 (Pituitary Adenylate Cyclase-Activating Polypeptide) RN - 0 (Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide) RN - 37221-79-7 (Vasoactive Intestinal Peptide) RN - 9007-12-9 (Calcitonin) RN - EC 4.6.1.1 (Adenylyl Cyclases) RN - JHB2QIZ69Z (Calcitonin Gene-Related Peptide) SB - IM MH - Adenylyl Cyclases/metabolism MH - Animals MH - Calcitonin/genetics MH - Calcitonin Gene-Related Peptide/*metabolism MH - Headache/*metabolism MH - Humans MH - Male MH - Migraine Disorders/metabolism MH - Neurons/metabolism MH - Pituitary Adenylate Cyclase-Activating Polypeptide/*metabolism MH - Rats, Sprague-Dawley MH - Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide/metabolism MH - Trigeminal Ganglion/*metabolism MH - Vasoactive Intestinal Peptide/metabolism OTO - NOTNLM OT - Botox OT - CGRP OT - PACAP OT - PACAP receptors OT - sensory nervous system OT - serotonin receptors EDAT- 2018/10/20 06:00 MHDA- 2019/03/08 06:00 CRDT- 2018/10/19 06:00 PHST- 2018/08/21 00:00 [received] PHST- 2018/09/28 00:00 [revised] PHST- 2018/10/02 00:00 [accepted] PHST- 2018/10/20 06:00 [pubmed] PHST- 2019/03/08 06:00 [medline] PHST- 2018/10/19 06:00 [entrez] AID - S0306-4522(18)30665-1 [pii] AID - 10.1016/j.neuroscience.2018.10.004 [doi] PST - ppublish SO - Neuroscience. 2018 Nov 21;393:319-332. doi: 10.1016/j.neuroscience.2018.10.004. Epub 2018 Oct 15.