ArticleThe Journal of pharmacology and experimental therapeutics2009
Differential activation of guinea pig intrinsic cardiac neurons by the PAC1 agonists maxadilan and pituitary adenylate cyclase-activating polypeptide 27 (PACAP27).
Article in The Journal of pharmacology and experimental therapeutics, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 28 citations in OpenAlex.
- Comparative specialization of intrinsic cardiac neurons in humans, mice and pigs.The Journal of physiology · 2025Article
- Biophysical modelling of intrinsic cardiac nervous system neuronal electrophysiology based on single-cell transcriptomics.The Journal of physiology · 2025Article
- Same same, but different: exploring the enigmatic role of the pituitary adenylate cyclase-activating polypeptide (PACAP) in invertebrate physiology.Journal of comparative physiology. A, Neuroethology, sensory, neural, and behavioral physiology · 2024Article
- Comparative specialization of intrinsic cardiac neurons in humans, mice, and pigs.bioRxiv : the preprint server for biology · 2024Article
- Vagally-mediated heart block after myocardial infarction associated with plasticity of epicardial neurons controlling the atrioventricular node.Frontiers in synaptic neuroscience · 2022Article
- PAC1 Receptor Internalization and Endosomal MEK/ERK Activation Is Essential for PACAP-Mediated Neuronal Excitability.Journal of molecular neuroscience : MN · 2021Review
- PACAP-Induced PAC1 Receptor Internalization and Recruitment of Endosomal Signaling Regulate Cardiac Neuron Excitability.Journal of molecular neuroscience : MN · 2019Review
- Article
- The Protective Role of PAC1-Receptor Agonist Maxadilan in BCCAO-Induced Retinal Degeneration.Journal of molecular neuroscience : MN · 2016Article
- Activation of MEK/ERK signaling contributes to the PACAP-induced increase in guinea pig cardiac neuron excitability.American journal of physiology. Cell physiology · 2016Article
- Activation of MEK/ERK Signaling by PACAP in Guinea Pig Cardiac Neurons.Journal of molecular neuroscience : MN · 2016Article
- PAC1R agonist maxadilan enhances hADSC viability and neural differentiation potential.Journal of cellular and molecular medicine · 2016Article
- Nickel suppresses the PACAP-induced increase in guinea pig cardiac neuron excitability.American journal of physiology. Cell physiology · 2015Article
- PAC₁ receptors mediate positive chronotropic responses to PACAP-27 and VIP in isolated mouse atria.European journal of pharmacology · 2013Article
- Pituitary adenylate cyclase 1 receptor internalization and endosomal signaling mediate the pituitary adenylate cyclase activating polypeptide-induced increase in guinea pig cardiac neuron excitability.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2013Article
- Pretreatment with nonselective cationic channel inhibitors blunts the PACAP-induced increase in guinea pig cardiac neuron excitability.Journal of molecular neuroscience : MN · 2012Article
- Immunohistochemical characterization of the intrinsic cardiac neural plexus in whole-mount mouse heart preparations.Heart rhythm · 2011Article
- Alternative splicing of the pituitary adenylate cyclase-activating polypetide (PACAP) receptor contributes to function of PACAP-27.Journal of molecular neuroscience : MN · 2010Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Pituitary adenylate cyclase-activating polypeptide (PACAP) evokes tachycardia followed by a larger cholinergic bradycardia in isolated guinea pig hearts. We used the selective PAC1 receptor agonist maxadilan and vasoactive intestinal polypeptide (VIP) to test the hypothesis that PACAP27-evoked tachycardia and bradycardia are mediated by VPAC and PAC1 receptors, respectively. Chronotropic actions of these peptides were evaluated in isolated perfused hearts. Direct neuronal actions were determined by intracellular voltage recordings from cholinergic neurons in atrial ganglion whole mounts. Administration of 1 nmol of PACAP27 to isolated hearts evoked typical biphasic rate responses, whereas 1 nmol of maxadilan caused only a minor rate decrease. Desensitization with VIP eliminated the positive chronotropic effect of PACAP27 selectively. Local application of PACAP27 to cardiac neurons frequently evoked slow depolarization and caused prolonged increase of neuronal excitability. Maxadilan rarely affected membrane potential but consistently increased excitability. VIP had no effect on excitability and evoked depolarization in only a few neurons. Because maxadilan increased neuronal excitability but did not trigger action potentials as PACAP often does, we evaluated the interaction of maxadilan with substance P (SP) in isolated hearts. SP depolarizes cardiac neurons more consistently than PACAP, often triggers neuronal action potentials, and causes bradycardia but does not increase neuronal excitability. Maxadilan had a persistent effect to augment negative chronotropic responses to SP. These findings support our hypothesis that PACAP evokes tachycardia and bradycardia through VPAC and PAC1 receptors, respectively. They also suggest that maxadilan and PACAP27 differ in activating PAC1 receptors on cardiac neurons and/or stimulating downstream signaling mechanisms.
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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.