ArticleFASEB journal : official publication of the Federation of American Societies for Experimental Biology2012
Signaling through the neuropeptide GPCR PAC₁ induces neuritogenesis via a single linear cAMP- and ERK-dependent pathway using a novel cAMP sensor.
Article in FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.
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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.
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Who cites it
48 citing papers in PubMed, 70 citations in OpenAlex.
- Activation and sensitization of meningeal nociceptors by PACAP-38: implications for migraine headache.Brain : a journal of neurology · 2026Article
- Activation of the pituitary adenylate cyclase-activating polypeptide type I receptor promotes neuroblastoma proliferation and migration through distinct G protein pathways.Cell communication and signaling : CCS · 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
- Intranasal administration of recombinant human BDNF as a potential therapy for some primary headaches.The journal of headache and pain · 2024Article
- Pituitary cyclase-activating polypeptide targeted treatments for the treatment of primary headache disorders.Annals of clinical and translational neurology · 2024Review
- The guanine nucleotide exchange factor RapGEF2 is required for ERK-dependent immediate-early gene (Egr1) activation during fear memory formation.Cellular and molecular life sciences : CMLS · 2024Article
- Molecular Mechanisms of Migraine: Nitric Oxide Synthase and Neuropeptides.International journal of molecular sciences · 2023Review
- Shared and independent roles of CGRP and PACAP in migraine pathophysiology.The journal of headache and pain · 2023Review
- ERK-dependent induction of the immediate-early gene Egr1 and the late gene Gpr50 contribute to two distinct phases of PACAP Gs-GPCR signaling for neuritogenesis.Journal of neuroendocrinology · 2022Article
- Neuropeptides and small-molecule amine transmitters: cooperative signaling in the nervous system.Cellular and molecular life sciences : CMLS · 2022Review
- Targeting VIP and PACAP Receptor Signaling: New Insights into Designing Drugs for the PACAP Subfamily of Receptors.International journal of molecular sciences · 2022Review
- The Role of Neuropeptide-Stimulated cAMP-EPACs Signalling in Cancer Cells.Molecules (Basel, Switzerland) · 2022Review
- Cyclic AMP-dependent activation of ERK via GLP-1 receptor signalling requires the neuroendocrine cell-specific guanine nucleotide exchanger NCS-RapGEF2.Journal of neuroendocrinology · 2021Article
- Cocaine-Dependent Acquisition of Locomotor Sensitization and Conditioned Place Preference Requires D1 Dopaminergic Signaling through a Cyclic AMP, NCS-Rapgef2, ERK, and Egr-1/Zif268 Pathway.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2021Article
- Pituitary Adenylate Cyclase-Activating Polypeptide (PACAP) Protects Striatal Cells and Improves Motor Function in Huntington's Disease Models: Role of PAC1 Receptor.Frontiers in pharmacology · 2021Article
- Molecular and cellular correlates of human nerve regeneration: ADCYAP1/PACAP enhance nerve outgrowth.Brain : a journal of neurology · 2020Article
- Beneficial Effects of Crocin against Depression via Pituitary Adenylate Cyclase-Activating Polypeptide.BioMed research international · 2020Article
- Activation of the VPAC2 Receptor Impairs Axon Outgrowth and Decreases Dendritic Arborization in Mouse Cortical Neurons by a PKA-Dependent Mechanism.Frontiers in neuroscience · 2020Article
- Chromaffin Cells of the Adrenal Medulla: Physiology, Pharmacology, and Disease.Comprehensive Physiology · 2019Article
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Both cAMP and ERK are necessary for neuroendocrine cell neuritogenesis, and pituitary adenylate cyclase-activating polypeptide (PACAP) activates each. It is important to know whether cAMP and ERK are arranged in a novel, linear pathway or in two parallel pathways using known signaling mechanisms. Native cellular responses [cAMP elevation, ERK phosphorylation, cAMP responsive element binding (CREB) phosphorylation, and neuritogenesis] and promoter-reporter gene activation after treatment with forskolin, cAMP analogs, and PACAP were measured in Neuroscreen-1 (NS-1) cells, a PC12 variant enabling simultaneous morphological, molecular biological, and biochemical analysis. Forskolin (25 μM) and cAMP analogs (8-bromo-cAMP, dibutyryl-cAMP, and 8-chlorophenylthio-cAMP) stimulated ERK phosphorylation and neuritogenesis in NS-1 cells. Both ERK phosphorylation and neuritogenesis were MEK dependent (blocked by 10 μM U0126) and PKA independent (insensitive to 30 μM H-89 or 100 nM myristoylated protein kinase A inhibitor). CREB phosphorylation induced by PACAP was blocked by H-89. The exchange protein activated by cAMP (Epac)-selective 8-(4-chlorophenylthio)-2'-O-Me-cAMP (100-500 μM) activated Rap1 without affecting the other cAMP-dependent processes. Thus, PACAP-38 potently stimulated two distinct and independent cAMP pathways leading to CREB or ERK activation in NS-1 cells. Drug concentrations for appropriate effect were derived from control data for all compounds. In summary, a novel PKA- and Epac-independent signaling pathway: PACAP → adenylate cyclase → cAMP → ERK → neuritogenesis has been identified.
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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.