Overview
Choose your reading level:
In plain language
PACAP-38 is a natural peptide of 38 amino acids found in the brain and nerves. It is a close relative of VIP and helps cells respond to stress.
It has become important in migraine research: when people with migraine are given PACAP, many have a migraine attack. Medicines that block PACAP are being tested to prevent migraines. PACAP itself is not a drug.
For students
PACAP (pituitary adenylate cyclase-activating polypeptide) was isolated in 1989 by Arimura and Miyata from sheep hypothalamus, based on its ability to raise cAMP in pituitary cells. PACAP-38 is the main form (about 4,534 Da); PACAP-27 is a shorter form. Its N-terminal region shares about 68% identity with VIP.
It acts through PAC1 (selective for PACAP), VPAC1 and VPAC2 receptors. It has roles in stress responses, circadian rhythm, nerve protection and blood vessel dilation.
For researchers and instructors
Migraine. Infusion of PACAP-38 provokes migraine-like attacks in many people with migraine, a model similar to CGRP provocation. Anti-PACAP monoclonal antibodies have been studied as preventives with encouraging early-phase results.
Neuroprotection. Protective effects in animal models of stroke, brain injury and retinal damage.
Psychiatry. PACAP–PAC1 signaling has been associated with PTSD risk in women in genetic studies.
Status. Natural neuropeptide; not a drug.
Molecular identity
- Amino acids
- 38
- Molecular weight
- ~4,534.3 Da
- Formula
- C₂₀₃H₃₃₁N₆₃O₅₃S
- Sequence
- HSDGIFTDSYSRYRKQMAVKKYLAAVLGKRYKQRVKNK-NH₂
Sequence map
Hydropathy
Kyte–Doolittle score per residue. Positive values are water-repelling.
Origin and history
PACAP was isolated in 1989 by Akira Arimura’s group at Tulane University from sheep hypothalamus. They named it for what it did: pituitary adenylate cyclase-activating polypeptide. It is closely related to VIP.
In 2009 researchers found that infusing PACAP-38 triggers migraine attacks in people with migraine, and drugs blocking PACAP are now in trials.
Key people
- Akira ArimuraTulane University
Timeline
- 1989
PACAP isolated
- 2009
Shown to trigger migraine attacks
- 2020s
Anti-PACAP migraine drugs in trials
See every peptide on one history timeline.
Human evidence
Infusing PACAP-38 can trigger migraine-like attacks in people with migraine, and drugs that block PACAP signaling are in clinical trials.
Registration and enrollment are not proof of benefit; check study results directly.
Explore original publications and distinguish preclinical findings from controlled human evidence.
Safety and regulatory status
See every compound on the regulatory tracker.
Natural neuropeptide; not a drug.
This profile is educational and does not provide treatment, dosing or sourcing guidance.
Sources
- PubMed literature search: PACAP-38
- PubChem compound search: PACAP-38
- PubMed: Miyata Arimura 1989 PACAP
- ClinicalTrials.gov search: PACAP-38
Hernandez Gener, E. (2026, November 7). PACAP-38: molecular data, research history and evidence. VALREXA Biosciences. https://valrexa.com/peptides/pacap-38.html
APA style · Last reviewed November 7, 2026 · Our editorial standardsLast reviewed November 7, 2026. Trial and regulatory status can change; confirm in the linked registries. This profile is educational and is not medical advice, a treatment recommendation, or dosing or sourcing guidance. Report an error · Corrections policy