PAC<sub>1</sub>, VPAC<sub>1</sub>, and VPAC<sub>2</sub> Receptor Expression in Rat and Human Trigeminal Ganglia: Characterization of PACAP-Responsive Receptor Antibodies

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,...

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Main Authors: Zoe Tasma, Andrew Siow, Paul W. R. Harris, Margaret A. Brimble, Simon J. O’Carroll, Debbie L. Hay, Christopher S. Walker
Format: Article
Language:English
Published: MDPI AG 2022-11-01
Series:International Journal of Molecular Sciences
Subjects:
Online Access:https://www.mdpi.com/1422-0067/23/22/13797
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author Zoe Tasma
Andrew Siow
Paul W. R. Harris
Margaret A. Brimble
Simon J. O’Carroll
Debbie L. Hay
Christopher S. Walker
author_facet Zoe Tasma
Andrew Siow
Paul W. R. Harris
Margaret A. Brimble
Simon J. O’Carroll
Debbie L. Hay
Christopher S. Walker
author_sort Zoe Tasma
collection DOAJ
description 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<sub>1n</sub> and PAC<sub>1s</sub> receptor splice variants. PAC<sub>1</sub>, VPAC<sub>1</sub>, and VPAC<sub>2</sub> receptor-like immunoreactivity were observed in subpopulations of both neuronal and glial-like cells in the TG. In this study, PAC<sub>1</sub>, VPAC<sub>1</sub>, and VPAC<sub>2</sub> 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.
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spelling doaj.art-3c985c4848b547de8c5767f2450c441c2023-11-24T08:33:34ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-11-0123221379710.3390/ijms232213797PAC<sub>1</sub>, VPAC<sub>1</sub>, and VPAC<sub>2</sub> Receptor Expression in Rat and Human Trigeminal Ganglia: Characterization of PACAP-Responsive Receptor AntibodiesZoe Tasma0Andrew Siow1Paul W. R. Harris2Margaret A. Brimble3Simon J. O’Carroll4Debbie L. Hay5Christopher S. Walker6School of Biological Sciences, The University of Auckland, Auckland 1010, New ZealandSchool of Biological Sciences, The University of Auckland, Auckland 1010, New ZealandSchool of Biological Sciences, The University of Auckland, Auckland 1010, New ZealandSchool of Biological Sciences, The University of Auckland, Auckland 1010, New ZealandDepartment of Anatomy and Medical Imaging, and Centre for Brain Research, Faculty of Medical and Health Science, The University of Auckland, Auckland 1023, New ZealandMaurice Wilkins Centre for Molecular Biodiscovery, The University of Auckland, Auckland 1010, New ZealandSchool of Biological Sciences, The University of Auckland, Auckland 1010, New ZealandPituitary 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<sub>1n</sub> and PAC<sub>1s</sub> receptor splice variants. PAC<sub>1</sub>, VPAC<sub>1</sub>, and VPAC<sub>2</sub> receptor-like immunoreactivity were observed in subpopulations of both neuronal and glial-like cells in the TG. In this study, PAC<sub>1</sub>, VPAC<sub>1</sub>, and VPAC<sub>2</sub> 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.https://www.mdpi.com/1422-0067/23/22/13797PACAPVIPPAC<sub>1</sub> receptorVPAC<sub>1</sub> receptorVPAC<sub>2</sub> receptormigraine
spellingShingle Zoe Tasma
Andrew Siow
Paul W. R. Harris
Margaret A. Brimble
Simon J. O’Carroll
Debbie L. Hay
Christopher S. Walker
PAC<sub>1</sub>, VPAC<sub>1</sub>, and VPAC<sub>2</sub> Receptor Expression in Rat and Human Trigeminal Ganglia: Characterization of PACAP-Responsive Receptor Antibodies
International Journal of Molecular Sciences
PACAP
VIP
PAC<sub>1</sub> receptor
VPAC<sub>1</sub> receptor
VPAC<sub>2</sub> receptor
migraine
title PAC<sub>1</sub>, VPAC<sub>1</sub>, and VPAC<sub>2</sub> Receptor Expression in Rat and Human Trigeminal Ganglia: Characterization of PACAP-Responsive Receptor Antibodies
title_full PAC<sub>1</sub>, VPAC<sub>1</sub>, and VPAC<sub>2</sub> Receptor Expression in Rat and Human Trigeminal Ganglia: Characterization of PACAP-Responsive Receptor Antibodies
title_fullStr PAC<sub>1</sub>, VPAC<sub>1</sub>, and VPAC<sub>2</sub> Receptor Expression in Rat and Human Trigeminal Ganglia: Characterization of PACAP-Responsive Receptor Antibodies
title_full_unstemmed PAC<sub>1</sub>, VPAC<sub>1</sub>, and VPAC<sub>2</sub> Receptor Expression in Rat and Human Trigeminal Ganglia: Characterization of PACAP-Responsive Receptor Antibodies
title_short PAC<sub>1</sub>, VPAC<sub>1</sub>, and VPAC<sub>2</sub> Receptor Expression in Rat and Human Trigeminal Ganglia: Characterization of PACAP-Responsive Receptor Antibodies
title_sort pac sub 1 sub vpac sub 1 sub and vpac sub 2 sub receptor expression in rat and human trigeminal ganglia characterization of pacap responsive receptor antibodies
topic PACAP
VIP
PAC<sub>1</sub> receptor
VPAC<sub>1</sub> receptor
VPAC<sub>2</sub> receptor
migraine
url https://www.mdpi.com/1422-0067/23/22/13797
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