5-HT4 and 5-HT2 receptors antagonistically influence gap junctional coupling between rat auricular myocytes

Derangeon, Mickaël; Bozon, Véronique; Defamie, Norah; Peineau, Nicolas; Bourmeyster, Nicolas; Sarrouilhe, Denis; Argibay, Jorge; Hervé, Jean-Claude

doi:10.1016/j.yjmcc.2009.07.005

Cited by 29 publications

(16 citation statements)

References 43 publications

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“…These structures mediate cell-cell communication in almost all tissues, but up to now, little has been known about their regulation by physiological stimuli. Acute exposures of ventricular myocytes to serotonin were recently seen (80) 3 to markedly enhance GJIC through activation of the RhoA downstream pathway. The present results provide further insight into the gating and regulation of junctional channels, confirm the important role of ZO-1 in the function of Cx43 gap junctions, and identify a new downstream target for the small G-protein RhoA.…”

Section: Journal Of Biological Chemistry 30761mentioning

confidence: 99%

RhoA GTPase and F-actin Dynamically Regulate the Permeability of Cx43-made Channels in Rat Cardiac Myocytes

Derangeon

Bourmeyster

Plaisance

et al. 2008

Journal of Biological Chemistry

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Gap junctions are clusters of transmembrane channels allowing a passive diffusion of ions and small molecules between adjacent cells. Connexin43, the main channel-forming protein expressed in ventricular myocytes, can associate with zonula occludens-1, a scaffolding protein linked to the actin cytoskeleton and to signal transduction molecules. The possible influence of Rho GTPases, major regulators of cellular junctions and of the actin cytoskeleton, in the modulation of gap junctional intercellular communication (GJIC) was examined. The activation of RhoA by cytoxic necrotizing factor 1 markedly enhanced GJIC, whereas its specific inhibition by the Clostridium botulinum C3 exoenzyme significantly reduced it. RhoA activity affects GJIC without major cellular redistribution of junctional plaques or changes in the Cx43 phosphorylation pattern. As these GTPases frequently act via the cortical cytoskeleton, the importance of F-actin in the modulation of GJIC was investigated by means of agents interfering with actin polymerization. Cytoskeleton stabilization by phalloidin slowed down the kinetics of channel rundown in the absence of ATP, whereas its disruption by cytochalasin D rapidly and markedly reduced GJIC despite ATP presence. Cytoskeleton stabilization by phalloidin markedly reduced the consequences of RhoA activation or inactivation. This mechanism appears to be the first described capable to both up-or down-regulate GJIC through RhoA activation or, conversely, inhibition. The inhibition of Rho downstream kinase effectors had no effect on GJIC. The present results provide further insight into the gating and regulation of junctional channels and identify a new downstream target for the small G-protein RhoA.

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Section: Journal Of Biological Chemistry 30761mentioning

confidence: 99%

RhoA GTPase and F-actin Dynamically Regulate the Permeability of Cx43-made Channels in Rat Cardiac Myocytes

Derangeon

Bourmeyster

Plaisance

et al. 2008

Journal of Biological Chemistry

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“…The serotonergic system has seven serotonin receptor proteins (5HT 1-7 ) and thirteen subtypes including 5HT2A/2B/2C receptors [8]. Both 5-HT2A and 5-HT1A receptors play an active role in anxiety-like behavior.…”

Section: Introductionmentioning

confidence: 99%

Stimulation of Anxiety-Like Behavior via ERK Pathway by Competitive Serotonin Receptors 2A and 1A in Post-Traumatic Stress Disordered Mice

Xiang

Jiang

et al. 2017

Neurosignals

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Background/Aims: Serotonin 5HT2A and 5HT1A receptors (5HT2AR, 5HT1AR) have the closest connection to anxiety-like behavior in post-traumatic stress disorder (PTSD). However, the underlying mechanism remains unclear. In this study, we explored the connection between 5HT2A and 5HT1A receptors and anxiety-like behavior. Methods: In the PTSD animal model, mice were exposed to conditioned fear stress coupled with single-prolonged stress (CF+SPS). Post stress infliction and behavioral tests, of which include open field, freezing behavior and elevated plus maze tests were carried out to examine establishment of the proposed model. Both Western blot analysis and immunofluorescence labeling were used to evaluate protein expressions of 5HT2AR, 5HT1AR, ERK1, ERK2 and c-Myc in the hippocampi of the mice and RT Q-PCR was employed for evaluation of the relative mRNA expressions. Results: Based on the model established utilizing the CF+SPS procedure, we found 5HT2AR to play a positive role on anxiety-like behavior by inhibiting the expression of 5HT1AR. In addition, the ERK-c-Myc pathway elicited the effect of 5HT2AR and 5HT1AR on anxiety-like behavior in PTSD, 5-HT enhanced the anxiety-like behavior through both 5HT2AR and 5HT1AR. Conclusion: These findings suggest competive interaction between 5HT2AR and 5HT1AR actively affects anxiety-like behavior in the hippocampi of PTSD mice via the ERK pathway.

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“…This serotonin-mediated attenuation of ghrelin signaling may potentially involve dimerization of the GHS-R1a and the 5-HT 2C receptor, which is a previously unexplored possibility under investigation here. Notably, serotonin receptors have been found to exist as oligomer complexes with other serotonin receptor family members (51), with metabotrophic glutamate receptors (52)(53)(54), and with dopamine receptors (55). However, oligomeric complex formation does not always translate into second messenger signaling effects, because downstream consequences were unaffected in a 5-HT 2A /mGlu 2 heterocomplex (54).…”

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confidence: 99%

Promiscuous Dimerization of the Growth Hormone Secretagogue Receptor (GHS-R1a) Attenuates Ghrelin-mediated Signaling

Schellekens

Oeffelen

Dinan

et al. 2013

Journal of Biological Chemistry

125

158

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Background:The ghrelin receptor (GHS-R1a) has multiple biological functionalities, including the regulation of appetite and hedonic food intake. Results: A novel GHS-R1a/5-HT 2C heterodimer was identified, in addition to GHS-R1a/D 1 and GHS-R1a/MC 3 . Conclusion: Promiscuous GHS-R1a receptor heterodimerization attenuates downstream signaling and affects trafficking depending on dimer partner. Significance: The existence of multiple GHS-R1a heterodimers has important consequences for the future development of therapeutics with enhanced specificity.

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5-HT4 and 5-HT2 receptors antagonistically influence gap junctional coupling between rat auricular myocytes

Cited by 29 publications

References 43 publications

RhoA GTPase and F-actin Dynamically Regulate the Permeability of Cx43-made Channels in Rat Cardiac Myocytes

RhoA GTPase and F-actin Dynamically Regulate the Permeability of Cx43-made Channels in Rat Cardiac Myocytes

Stimulation of Anxiety-Like Behavior via ERK Pathway by Competitive Serotonin Receptors 2A and 1A in Post-Traumatic Stress Disordered Mice

Promiscuous Dimerization of the Growth Hormone Secretagogue Receptor (GHS-R1a) Attenuates Ghrelin-mediated Signaling

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