ReviewJournal of molecular neuroscience : MN2021
PAC1 Receptor Internalization and Endosomal MEK/ERK Activation Is Essential for PACAP-Mediated Neuronal Excitability.
Review in Journal of molecular neuroscience : MN, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
21 citing papers in PubMed, 36 citations in OpenAlex.
- Structural basis of β-arrestin coupling and transducer selectivity in PAC1R.Acta pharmacologica Sinica · 2026Article
- The ventral hippocampus to paraventricular thalamus circuit regulates context-dependent hyperlocomotion through PAC1 receptor signaling in the chronic stress-induced PTSD mouse model.Translational psychiatry · 2026Article
- Cartilage degradation is followed by PAC1 receptor reduction in articular cartilage of human knee joints.GeroScience · 2026Article
- PAC1 receptor agonist maxadilan alleviates corneal inflammation in a murine model of LPS-induced ocular inflammation.PloS one · 2026Article
- PACAP versus CGRP in migraine: From mouse models to clinical translation.Cephalalgia : an international journal of headache · 2025Review
- Pituitary adenylate cyclase-activating polypeptide signalling as a therapeutic target in migraine.Nature reviews. Neurology · 2024Review
- Dipeptidyl Peptidase (DPP)-4 Inhibitors and Pituitary Adenylate Cyclase-Activating Polypeptide, a DPP-4 Substrate, Extend Neurite Outgrowth of Mouse Dorsal Root Ganglia Neurons: A Promising Approach in Diabetic Polyneuropathy Treatment.International journal of molecular sciences · 2024Article
- Hippocampal PACAP signaling activation triggers a rapid antidepressant response.Military Medical Research · 2024Article
- PACAP/PAC1-R activation contributes to hyperalgesia in 6-OHDA-induced Parkinson's disease model rats via promoting excitatory synaptic transmission of spinal dorsal horn neurons.Acta pharmacologica Sinica · 2023Article
- PACAP6-38 improves nitroglycerin-induced central sensitization by modulating synaptic plasticity at the trigeminal nucleus caudalis in a male rat model of chronic migraine.The journal of headache and pain · 2023Article
- Shared and independent roles of CGRP and PACAP in migraine pathophysiology.The journal of headache and pain · 2023Review
- Increased pituitary adenylate cyclase-activating peptide genes expression in the prefrontal cortex in schizophrenia in relation to suicide.Frontiers in molecular neuroscience · 2023Article
- Neuropeptides and small-molecule amine transmitters: cooperative signaling in the nervous system.Cellular and molecular life sciences : CMLS · 2022Review
- First-in-human development of a pharmacodynamic biomarker for PACClinical and translational science · 2022Article
- Homer signaling pathways as effective therapeutic targets for ischemic and traumatic brain injuries and retinal lesions.Neural regeneration research · 2022Review
- GPCR Intracellular Loop Regulation of Beta-Arrestin-Mediated Endosomal Signaling Dynamics.Journal of molecular neuroscience : MN · 2022Article
- Pituitary adenylate cyclase-activating polypeptide receptor activation in the hypothalamus recruits unique signaling pathways involved in energy homeostasis.American journal of physiology. Endocrinology and metabolism · 2022Article
- Female reproductive functions of the neuropeptide PACAP.Frontiers in endocrinology · 2022Review
- Vagally-mediated heart block after myocardial infarction associated with plasticity of epicardial neurons controlling the atrioventricular node.Frontiers in synaptic neuroscience · 2022Article
- Protective Effects of PACAP in a Rat Model of Diabetic Neuropathy.International journal of molecular sciences · 2021Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Pituitary adenylate cyclase activating polypeptide (PACAP, Adcyap1) activation of PAC1 receptors (Adcyap1r1) can significantly increase the excitability of diverse neurons through differential mechanisms. For guinea pig cardiac neurons, the modulation of excitability can be mediated in part by PAC1 receptor plasma membrane G protein-dependent activation of adenylyl cyclase and downstream signaling cascades. By contrast, PAC1 receptor-mediated excitability of hippocampal dentate gyrus granule cells appears independent of membrane-delimited AC/cAMP/PKA and PLC/PKC signaling. For both neuronal types, there is mechanistic convergence demonstrating that endosomal PAC1 receptor signaling has prominent roles. In these models, neuronal exposure to Pitstop2 to inhibit β-arrestin/clathrin-mediated PAC1 receptor internalization eliminates PACAP modulation of excitability. β-arrestin is a scaffold for a number of effectors especially MEK/ERK and notably, paradigms that inhibit PAC1 receptor endosome formation and ERK signaling also blunt the PACAP-induced increase in excitability. Detailed PAC1 receptor internalization and endosomal ERK signaling mechanisms have been confirmed in HEK PAC1R-EGFP cells and shown to be long lasting which appear to recapitulate the sustained electrophysiological responses. Thus, PAC1 receptor internalization/endosomal recruitment efficiently and efficaciously activates MEK/ERK signaling and appears to represent a singular and critical common denominator in regulating neuronal excitability by PACAP.
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What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.