2. Signaling Pathways
  3. GPCR/G Protein
  4. PACAP Receptor
  5. PAC1 Receptor Isoform

PAC1 Receptor

The pituitary adenylate cyclase-activating polypeptide type I receptor (PAC1R) is a high-affinity, PACAP-selective G protein-coupled receptor that regulates cellular survival and homeostasis in both central and peripheral nervous systems[1][2]. Activation of PAC1R engages multiple intracellular pathways, including adenylyl cyclase/cAMP, phospholipase C, MEK/ERK, p38 MAPK, and Akt, leading to modulation of neuronal excitability, neuroprotection, and anti-apoptotic effects[1][3]. Compared with related VPAC1 and VPAC2 receptors, PAC1R exhibits exclusive PACAP binding, distinct intracellular signaling dynamics, and involvement in endosomal signaling microstates that influence chronic pain and stress responses[4][5][6]. In disease models, PAC1R signaling has demonstrated neuroprotective roles in stroke, retinal injury, neurodegenerative disorders, and chronic pain, while maladaptive activation contributes to migraine, PTSD, and metabolic disorders[1][7][8][9]. Selective agonists, such as maxadilan, enhance stem cell viability, migration, and neural differentiation by activating PAC1R-mediated Wnt/β-catenin and PKA pathways[2]. Conversely, PAC1R antagonists and biased inhibitors targeting endosomal signaling are being explored for chronic pain, stress-related disorders, and migraine therapeutics[9][5]. Structural and pharmacophore analyses of PAC1R facilitate the design of peptide and small-molecule modulators with isoform-selective activity, providing practical frameworks for experimental and therapeutic applications[4][10].

References:

PAC1 Receptor Related Products (2):

Cat. No. Product Name Effect Purity
  • HY-147557
    PA-915
    		Antagonist 99.17%
    PA-915 (PAC1R antagonist 1) is a potent and orally active antagonist of PAC1 receptor. PA-915 inhibits pituitary adenylate cyclase-activating polypeptide (PACAP)-induced CREB phosphorylation. PA-915 can inhibit PACAP- and nerve injury-induced allodynia. PA-915 can be used for the research of neuropathic pain.
  • HY-P3483
    Maxadilan
    		Agonist
    Maxadilan is a specific irreversible PAC1 receptor agonist and a potent vasodilator peptide present in the salivary glands of sand flies. Maxadilan exhibits anti-apoptotic activity in hADSCs. Maxadilan inhibits pro-inflammatory cytokines (TNF-α) and enhances anti-inflammatory mediators (IL-10). Maxadilan can activate leukocytes and inhibit vascular permeability through PAC1 receptors. Maxadilan promotes neural differentiation of human adipose-derived stem cells. Maxadilan can be used to study endotoxin shock, atherosclerosis, and neurodegenerative diseases[1][2][3][4][5].