Pituitary Adenylate Cyclase-Activating Peptide
38-amino acid neuropeptide with neuroprotective, vasodilatory, and immunomodulatory effects through VPAC and PAC1 receptors.
Chemical Identity
| Property | Value |
|---|---|
| Chemical Formula | C203H331N63O53S |
| Molecular Weight | 4586 Da |
| Peptide Class | Neuropeptide (38 or 27 amino acids) |
| Forms | PACAP-38 (major), PACAP-27 (minor) |
| Sequence | HSDGIFTDSYSRYRKQMAVKKYLAAVLGKRYKQRVKNK-NH2 |
Structure
Pituitary adenylate cyclase-activating peptide (PACAP) exists as PACAP-38 (38 amino acids, 90% of tissues) and PACAP-27 (27 amino acids). It belongs to the VIP-secretin-glucagon family and shares 68% homology with VIP. The N-terminal 27 amino acids are identical in both forms and sufficient for receptor binding.
Mechanism of Action
PACAP binds PAC1 receptor (PACAP-selective) with high affinity, and VPAC1/VPAC2 receptors (shared with VIP) with lower affinity. PAC1 activation stimulates adenylyl cyclase and phospholipase C, increasing cAMP and IP3. This mediates neuroprotection, vasodilation, hormone release, and immune modulation.
Clinical Applications
- Migraine: PACAP-38 infusion triggers migraine (therapeutic target)
- Neuroprotection: Ischemic brain injury, neurodegenerative diseases
- ADHD: PAC1 receptor variants associated with ADHD
- Inflammatory diseases: Anti-inflammatory and immunomodulatory
- Reproduction: Gonadotropin regulation
Pharmacology
- Half-life: 2-5 minutes (rapid proteolytic degradation)
- Distribution: Hypothalamus, gut, adrenal medulla, immune cells
- PAC1: PACAP-selective (1000x higher affinity than VIP)
- DPP-4: Inactivated by DPP-4
References
- Miyata, A., et al. (1989). PACAP: a novel hypothalamic neuropeptide. Biochemical and Biophysical Research Communications, 164, 567-574.
- Tajti, J., et al. (2018). PACAP and migraine. Cephalalgia, 38, 35-45.
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