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,...
Main Authors: | , , , , , , |
---|---|
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 |
_version_ | 1797465154356510720 |
---|---|
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. |
first_indexed | 2024-03-09T18:17:31Z |
format | Article |
id | doaj.art-3c985c4848b547de8c5767f2450c441c |
institution | Directory Open Access Journal |
issn | 1661-6596 1422-0067 |
language | English |
last_indexed | 2024-03-09T18:17:31Z |
publishDate | 2022-11-01 |
publisher | MDPI AG |
record_format | Article |
series | International Journal of Molecular Sciences |
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 |
work_keys_str_mv | AT zoetasma pacsub1subvpacsub1subandvpacsub2subreceptorexpressioninratandhumantrigeminalgangliacharacterizationofpacapresponsivereceptorantibodies AT andrewsiow pacsub1subvpacsub1subandvpacsub2subreceptorexpressioninratandhumantrigeminalgangliacharacterizationofpacapresponsivereceptorantibodies AT paulwrharris pacsub1subvpacsub1subandvpacsub2subreceptorexpressioninratandhumantrigeminalgangliacharacterizationofpacapresponsivereceptorantibodies AT margaretabrimble pacsub1subvpacsub1subandvpacsub2subreceptorexpressioninratandhumantrigeminalgangliacharacterizationofpacapresponsivereceptorantibodies AT simonjocarroll pacsub1subvpacsub1subandvpacsub2subreceptorexpressioninratandhumantrigeminalgangliacharacterizationofpacapresponsivereceptorantibodies AT debbielhay pacsub1subvpacsub1subandvpacsub2subreceptorexpressioninratandhumantrigeminalgangliacharacterizationofpacapresponsivereceptorantibodies AT christopherswalker pacsub1subvpacsub1subandvpacsub2subreceptorexpressioninratandhumantrigeminalgangliacharacterizationofpacapresponsivereceptorantibodies |