ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2013
Pituitary adenylate cyclase 1 receptor internalization and endosomal signaling mediate the pituitary adenylate cyclase activating polypeptide-induced increase in guinea pig cardiac neuron excitability.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
54 citing papers in PubMed, 103 citations in OpenAlex.
- Article
- β-arrestin1 orchestrates endosomal signaling to regulate translational control of circadian light entrainment.Communications biology · 2026Article
- Cartilage degradation is followed by PAC1 receptor reduction in articular cartilage of human knee joints.GeroScience · 2026Article
- Structure-Encoded Location Biased Signaling in a Class B GPCR: Focus on the PTH Type 1 Receptor.Handbook of experimental pharmacology · 2026Review
- Associations between PACAP levels and psychophysiological indicators of fear and arousal in adults with posttraumatic stress symptoms.Journal of mood and anxiety disorders · 2025Article
- Chemical biology approaches to resolve the subcellular GPCR signaling landscape.Nature chemical biology · 2025Review
- EGFR-dependent endocytosis of Wnt9a and Fzd9b promotes β-catenin signaling during hematopoietic stem cell development in zebrafish.Science signaling · 2024Article
- β-Arrestin-independent endosomal cAMP signaling by a polypeptide hormone GPCR.Nature chemical biology · 2024Article
- Soluble cyclase-mediated nuclear cAMP synthesis is sufficient for cell proliferation.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Novel Fluorescently Labeled PACAP and VIP Highlight Differences between Peptide Internalization and Receptor Pharmacology.ACS pharmacology & translational science · 2023Article
- Endosomal parathyroid hormone receptor signaling.American journal of physiology. Cell physiology · 2022Review
- GPCR Intracellular Loop Regulation of Beta-Arrestin-Mediated Endosomal Signaling Dynamics.Journal of molecular neuroscience : MN · 2022Article
- Effects of the clathrin inhibitor Pitstop-2 on synaptic vesicle recycling at a central synapseFrontiers in synaptic neuroscience · 2022Article
- The PACAP/PAC1 Receptor System and Feeding.Brain sciences · 2021Review
- Review
- PAC1 Receptor Internalization and Endosomal MEK/ERK Activation Is Essential for PACAP-Mediated Neuronal Excitability.Journal of molecular neuroscience : MN · 2021Review
- FluoSTEPs: Fluorescent biosensors for monitoring compartmentalized signaling within endogenous microdomains.Science advances · 2021Article
- PACAP-PAC1 Signaling Regulates Serotonin 2A Receptor Internalization.Frontiers in endocrinology · 2021Article
- PTH1R Actions on Bone Using the cAMP/Protein Kinase A Pathway.Frontiers in endocrinology · 2021Review
- Pituitary Adenylate Cyclase-Activating Polypeptide in Learning and Memory.Frontiers in cellular neuroscience · 2021Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
After G-protein-coupled receptor activation and signaling at the plasma membrane, the receptor complex is often rapidly internalized via endocytic vesicles for trafficking into various intracellular compartments and pathways. The formation of signaling endosomes is recognized as a mechanism that produces sustained intracellular signals that may be distinct from those generated at the cell surface for cellular responses including growth, differentiation, and survival. Pituitary adenylate cyclase activating polypeptide (PACAP; Adcyap1) is a potent neurotransmitter/neurotrophic peptide and mediates its diverse cellular functions in part through internalization of its cognate G-protein-coupled PAC1 receptor (PAC1R; Adcyap1r1). In the present study, we examined whether PAC1R endocytosis participates in the regulation of neuronal excitability. Although PACAP increased excitability in 90% of guinea pig cardiac neurons, pretreatment with Pitstop 2 or dynasore to inhibit clathrin and dynamin I/II, respectively, suppressed the PACAP effect. Subsequent addition of inhibitor after the PACAP-induced increase in excitability developed gradually attenuated excitability with no changes in action potential properties. Likewise, the PACAP-induced increase in excitability was markedly decreased at ambient temperature. Receptor trafficking studies with GFP-PAC1 cell lines demonstrated the efficacy of Pitstop 2, dynasore, and low temperatures at suppressing PAC1R endocytosis. In contrast, brefeldin A pretreatments to disrupt Golgi vesicle trafficking did not blunt the PACAP effect, and PACAP/PAC1R signaling still increased neuronal cAMP production even with endocytic blockade. Our results demonstrate that PACAP/PAC1R complex endocytosis is a key step for the PACAP modulation of cardiac neuron excitability.
Indexed as
Identifiers
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.