PACAP-38
preclinicalAlso known as: Pituitary adenylate cyclase-activating polypeptide
PACAP-38 (pituitary adenylate cyclase-activating polypeptide) is a 38-amino acid neuropeptide belonging to the vasoactive intestinal peptide (VIP)/secretin family. Its primary mechanism of action involves high-affinity binding to the PAC1 receptor, a G protein-coupled receptor that activates adenylate cyclase, leading to increased cyclic AMP (cAMP) levels. This signaling cascade mediates neuroprotective effects, including inhibition of apoptosis, modulation of neuroinflammation, and promotion of neuronal survival. Additionally, PACAP-38 exerts vasoregulatory functions by inducing vasodilation in cerebral and peripheral vasculature, partly through nitric oxide-dependent pathways. Preclinical research (over 3,100 PubMed-indexed studies) has demonstrated PACAP-38's efficacy in models of ischemic stroke, traumatic brain injury, and neurodegenerative diseases such as Parkinson's and Alzheimer's. It reduces infarct volume, attenuates oxidative stress, and supports blood-brain barrier integrity. In migraine models, PACAP-38 infusion triggers headache-like responses, implicating PAC1 receptors in migraine pathophysiology. Studies also highlight its role in stress adaptation, circadian rhythm regulation, and neuroendocrine modulation. Despite robust preclinical evidence, PACAP-38 remains in the preclinical stage, with no approved clinical applications. Its therapeutic potential is limited by rapid enzymatic degradation and poor blood-brain barrier penetration. Ongoing research focuses on developing stable analogs, receptor-selective agonists, and delivery systems to translate these neuroprotective and vasoregulatory properties into viable treatments for neurological and vascular disorders. For research purposes only — not medical advice.
Key data
C203H331N63O53SResearch & studies
PACAP infusions can provoke migraine attacks in patients.; A monoclonal antibody against the PACAP-receptor failed in a placebo-controlled study.; Lu AG09222 reduced monthly migraine days versus placebo but did not meet the 50% reduction endpoint.; The PROCEED study, testing four doses of Lu AG09222, is expected to complete in 2025.
PACAP AAV injection increased PACAP-27 levels specifically in the PVT.; PACAP overexpression reduced ethanol drinking and preference under intermittent access.; No significant differences were observed in sucrose drinking/preference or most affective behaviors.; Rats with PACAP overexpression spent less time swimming in the forced swim test.
PACAP is a key neurotransmitter in the adrenal medulla that provokes strong secretory responses from chromaffin cells.; The cellular mechanisms underlying PACAP-stimulated secretion remain poorly understood.; PACAP acts alongside acetylcholine to regulate hormone release, including epinephrine and norepinephrine.
PACAP-deficient mice show longer AIS length in layer 2/3 pyramidal neurons of the primary somatosensory barrel field.; Repeated atomoxetine treatment improved AIS abnormality and hyperactivity in PACAP-deficient mice.; AIS abnormalities are associated with neurodevelopmental disorder-like behaviors in PACAP-deficient mice.
Frequently asked questions
What is PACAP-38?
PACAP-38 (pituitary adenylate cyclase-activating polypeptide) is a 38-amino acid neuropeptide belonging to the vasoactive intestinal peptide (VIP)/secretin family. Its primary mechanism of action involves high-affinity binding to the PAC1 receptor, a G protein-coupled receptor that activates adenylate cyclase, leading
How does PACAP-38 work?
38-aa neuropeptide of the VIP/secretin family acting on PAC1 receptors; neuroprotective and vasoregulatory.
What is the research status of PACAP-38?
PACAP-38 is currently classified as preclinical, with 3,124 research references on record. This is for research purposes only and is not medical advice.
What is the molecular weight of PACAP-38?
PACAP-38 has a molecular weight of approximately 4534 g/mol (formula C203H331N63O53S).
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