Transport of the pituitary adenylate cyclase-activating polypeptide across the blood-brain barrier: implications for migraine
Abstract Background Pituitary adenylate cyclase-activating polypeptide (PACAP) is widely distributed in the nervous system and is involved in migraine pathophysiology. Understanding the function of the blood-brain barrier (BBB) in relation to PACAP is important to the understand the mechanisms behin...
| Main Authors: | , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2018-05-01
|
| Series: | The Journal of Headache and Pain |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s10194-018-0861-3 |
| _version_ | 1818021684000587776 |
|---|---|
| author | Faisal Mohammad Amin Henrik Winther Schytz |
| author_facet | Faisal Mohammad Amin Henrik Winther Schytz |
| author_sort | Faisal Mohammad Amin |
| collection | DOAJ |
| description | Abstract Background Pituitary adenylate cyclase-activating polypeptide (PACAP) is widely distributed in the nervous system and is involved in migraine pathophysiology. Understanding the function of the blood-brain barrier (BBB) in relation to PACAP is important to the understand the mechanisms behind PACAP-induced migraine attacks, but also to develop antimigraine drugs targeting the PACAP receptors Here, we aim to review the transport ability of PACAP across the BBB. Methods We performed a systematic literature search on PubMed to identify studies reporting original data on PACAP and BBB. The search was finalized in July 2017. Results The literature search identified 96 papers of which 11 contained relevant data. In addition, two papers were known to be relevant and were included. A total of 13 papers studies were included in the final analysis. Preclinical studies (n = 10) suggest the existence of specific PACAP transport systems across the BBB, while human PACAP studies failed to show vasodilator effect of PACAP on the cerebral arteries from the lumen (n = 3). Conclusion PACAP38 is transported over the BBB actively, while PACAP27 cross the BBB by diffusion over the membrane, but after crossing the endothelial membrane both isoforms are either rapidly degraded or efflux back from brain to blood. Thus, a direct central action of the PACAPs is unlikely. This is supported by studies showing selective PACAP effect on extra-cerebral arteries. |
| first_indexed | 2024-04-14T08:21:04Z |
| format | Article |
| id | doaj.art-8b0cb5e710694bf082a5f2bd72b45204 |
| institution | Directory Open Access Journal |
| issn | 1129-2369 1129-2377 |
| language | English |
| last_indexed | 2024-04-14T08:21:04Z |
| publishDate | 2018-05-01 |
| publisher | BMC |
| record_format | Article |
| series | The Journal of Headache and Pain |
| spelling | doaj.art-8b0cb5e710694bf082a5f2bd72b452042022-12-22T02:04:12ZengBMCThe Journal of Headache and Pain1129-23691129-23772018-05-011911610.1186/s10194-018-0861-3Transport of the pituitary adenylate cyclase-activating polypeptide across the blood-brain barrier: implications for migraineFaisal Mohammad Amin0Henrik Winther Schytz1Danish Headache Center, Department of Neurology, Rigshospitalet Glostrup, University of CopenhagenDanish Headache Center, Department of Neurology, Rigshospitalet Glostrup, University of CopenhagenAbstract Background Pituitary adenylate cyclase-activating polypeptide (PACAP) is widely distributed in the nervous system and is involved in migraine pathophysiology. Understanding the function of the blood-brain barrier (BBB) in relation to PACAP is important to the understand the mechanisms behind PACAP-induced migraine attacks, but also to develop antimigraine drugs targeting the PACAP receptors Here, we aim to review the transport ability of PACAP across the BBB. Methods We performed a systematic literature search on PubMed to identify studies reporting original data on PACAP and BBB. The search was finalized in July 2017. Results The literature search identified 96 papers of which 11 contained relevant data. In addition, two papers were known to be relevant and were included. A total of 13 papers studies were included in the final analysis. Preclinical studies (n = 10) suggest the existence of specific PACAP transport systems across the BBB, while human PACAP studies failed to show vasodilator effect of PACAP on the cerebral arteries from the lumen (n = 3). Conclusion PACAP38 is transported over the BBB actively, while PACAP27 cross the BBB by diffusion over the membrane, but after crossing the endothelial membrane both isoforms are either rapidly degraded or efflux back from brain to blood. Thus, a direct central action of the PACAPs is unlikely. This is supported by studies showing selective PACAP effect on extra-cerebral arteries.http://link.springer.com/article/10.1186/s10194-018-0861-3MigrainePACAPBlood-brain barrier |
| spellingShingle | Faisal Mohammad Amin Henrik Winther Schytz Transport of the pituitary adenylate cyclase-activating polypeptide across the blood-brain barrier: implications for migraine The Journal of Headache and Pain Migraine PACAP Blood-brain barrier |
| title | Transport of the pituitary adenylate cyclase-activating polypeptide across the blood-brain barrier: implications for migraine |
| title_full | Transport of the pituitary adenylate cyclase-activating polypeptide across the blood-brain barrier: implications for migraine |
| title_fullStr | Transport of the pituitary adenylate cyclase-activating polypeptide across the blood-brain barrier: implications for migraine |
| title_full_unstemmed | Transport of the pituitary adenylate cyclase-activating polypeptide across the blood-brain barrier: implications for migraine |
| title_short | Transport of the pituitary adenylate cyclase-activating polypeptide across the blood-brain barrier: implications for migraine |
| title_sort | transport of the pituitary adenylate cyclase activating polypeptide across the blood brain barrier implications for migraine |
| topic | Migraine PACAP Blood-brain barrier |
| url | http://link.springer.com/article/10.1186/s10194-018-0861-3 |
| work_keys_str_mv | AT faisalmohammadamin transportofthepituitaryadenylatecyclaseactivatingpolypeptideacrossthebloodbrainbarrierimplicationsformigraine AT henrikwintherschytz transportofthepituitaryadenylatecyclaseactivatingpolypeptideacrossthebloodbrainbarrierimplicationsformigraine |