PMID- 36430275 OWN - NLM STAT- MEDLINE DCOM- 20221129 LR - 20221213 IS - 1422-0067 (Electronic) IS - 1422-0067 (Linking) VI - 23 IP - 22 DP - 2022 Nov 9 TI - PAC(1), VPAC(1), and VPAC(2) Receptor Expression in Rat and Human Trigeminal Ganglia: Characterization of PACAP-Responsive Receptor Antibodies. LID - 10.3390/ijms232213797 [doi] LID - 13797 AB - Pituitary adenylate cyclase-activating peptide (PACAP) is a neuropeptide expressed in the trigeminal ganglia (TG). The TG conducts nociceptive signals in the head and may play roles in migraine. PACAP infusion provokes headaches in healthy individuals and migraine-like attacks in patients; however, it is not clear whether targeting this system could be therapeutically efficacious. To effectively target the PACAP system, an understanding of PACAP receptor distribution is required. Therefore, this study aimed to characterize commercially available antibodies and use these to detect PACAP-responsive receptors in the TG. Antibodies were initially validated in receptor transfected cell models and then used to explore receptor expression in rat and human TG. Antibodies were identified that could detect PACAP-responsive receptors, including the first antibody to differentiate between the PAC(1n) and PAC(1s) receptor splice variants. PAC(1), VPAC(1), and VPAC(2) receptor-like immunoreactivity were observed in subpopulations of both neuronal and glial-like cells in the TG. In this study, PAC(1), VPAC(1), and VPAC(2) receptors were detected in the TG, suggesting they are all potential targets to treat migraine. These antibodies may be useful tools to help elucidate PACAP-responsive receptor expression in tissues. However, most antibodies exhibited limitations, requiring the use of multiple methodologies and the careful inclusion of controls. FAU - Tasma, Zoe AU - Tasma Z AUID- ORCID: 0000-0002-7652-6004 AD - School of Biological Sciences, The University of Auckland, Auckland 1010, New Zealand. FAU - Siow, Andrew AU - Siow A AUID- ORCID: 0000-0002-0341-065X AD - School of Biological Sciences, The University of Auckland, Auckland 1010, New Zealand. AD - School of Chemical Sciences, The University of Auckland, Auckland 1010, New Zealand. FAU - Harris, Paul W R AU - Harris PWR AD - School of Biological Sciences, The University of Auckland, Auckland 1010, New Zealand. AD - School of Chemical Sciences, The University of Auckland, Auckland 1010, New Zealand. AD - Maurice Wilkins Centre for Molecular Biodiscovery, The University of Auckland, Auckland 1010, New Zealand. FAU - Brimble, Margaret A AU - Brimble MA AUID- ORCID: 0000-0002-7086-4096 AD - School of Biological Sciences, The University of Auckland, Auckland 1010, New Zealand. AD - School of Chemical Sciences, The University of Auckland, Auckland 1010, New Zealand. AD - Maurice Wilkins Centre for Molecular Biodiscovery, The University of Auckland, Auckland 1010, New Zealand. FAU - O'Carroll, Simon J AU - O'Carroll SJ AUID- ORCID: 0000-0003-1628-4864 AD - Department of Anatomy and Medical Imaging, and Centre for Brain Research, Faculty of Medical and Health Science, The University of Auckland, Auckland 1023, New Zealand. FAU - Hay, Debbie L AU - Hay DL AUID- ORCID: 0000-0002-9558-5122 AD - Maurice Wilkins Centre for Molecular Biodiscovery, The University of Auckland, Auckland 1010, New Zealand. AD - Department of Pharmacology and Toxicology, The University of Otago, Dunedin 9016, New Zealand. FAU - Walker, Christopher S AU - Walker CS AUID- ORCID: 0000-0001-8151-4123 AD - School of Biological Sciences, The University of Auckland, Auckland 1010, New Zealand. AD - Maurice Wilkins Centre for Molecular Biodiscovery, The University of Auckland, Auckland 1010, New Zealand. LA - eng GR - N/A/Royal Society of New Zealand/ GR - N/A/Health Research Council, New Zealand/ PT - Journal Article DEP - 20221109 PL - Switzerland TA - Int J Mol Sci JT - International journal of molecular sciences JID - 101092791 RN - 0 (Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide) RN - 0 (Pituitary Adenylate Cyclase-Activating Polypeptide) RN - 0 (Antibodies) SB - IM MH - Humans MH - Rats MH - Animals MH - Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide/genetics/metabolism MH - *Pituitary Adenylate Cyclase-Activating Polypeptide/metabolism MH - Trigeminal Ganglion/metabolism MH - Gene Expression MH - Antibodies MH - *Migraine Disorders/genetics PMC - PMC9697343 OTO - NOTNLM OT - PAC1 receptor OT - PACAP OT - VIP OT - VPAC1 receptor OT - VPAC2 receptor OT - migraine OT - trigeminal ganglia COIS- Debbie L. Hay is or has been a consultant or speaker for Lilly, Amgen, Teva, Intarcia, Merck Sharp & Dohme and has received research funding from Living Cell Technologies (Sydney, Australia) and Abbvie Inc. (Mettawa, IL USA.) in the past three years. Christopher S. Walker has received research support from Living Cell Technologies and Abbvie Inc. EDAT- 2022/11/27 06:00 MHDA- 2022/11/30 06:00 PMCR- 2022/11/09 CRDT- 2022/11/26 01:15 PHST- 2022/09/29 00:00 [received] PHST- 2022/11/02 00:00 [revised] PHST- 2022/11/06 00:00 [accepted] PHST- 2022/11/26 01:15 [entrez] PHST- 2022/11/27 06:00 [pubmed] PHST- 2022/11/30 06:00 [medline] PHST- 2022/11/09 00:00 [pmc-release] AID - ijms232213797 [pii] AID - ijms-23-13797 [pii] AID - 10.3390/ijms232213797 [doi] PST - epublish SO - Int J Mol Sci. 2022 Nov 9;23(22):13797. doi: 10.3390/ijms232213797.