5-HT Receptor Regulation of Neurotransmitter Release

Fink, Klaus; Göthert, M.

doi:10.1124/pr.59.07103

Cited by 325 publications

(75 citation statements)

References 280 publications

(377 reference statements)

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“…5-HTR4 is positively coupled to adenylyl cyclase, increasing levels of cAMP when the receptor is stimulated. 5-HTR4 is highly expressed in the rodent cortex, striatum, hippocampus, septum, and amygdala (Waeber et al, 1996;Varnäs et al, 2003), and is located postsynaptically where it modulates neurotransmitter (e.g., acetylcholine) release from the postsynaptic cell (Fink and Göthert, 2007). We find that cells that express 5-HTR4 invariably coexpress p11, in brain regions relevant to major depression, demonstrating that this interaction is physiologically relevant.…”

Section: Discussionmentioning

confidence: 65%

Role of p11 in Cellular and Behavioral Effects of 5-HT4 Receptor Stimulation

Warner-Schmidt¹,

Flajolet²,

Maller³

et al. 2009

J. Neurosci.

155

171

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p11 (S100A10), a member of a large family of S100 proteins, interacts with serotonin receptor 1B (5-HTR1B), modulates 5-HT1B receptor signal transduction, and is required for antidepressant responses to activation of this receptor. In the current study, we investigated the specificity of the interaction between 5-HTR1B and p11 by screening brain-expressed S100 proteins against serotonin and noradrenergic receptors. The data indicate that p11 is unique among its family members for its interactions with defined serotonin receptors. We identify a novel p11-interacting receptor (5-HTR4) and characterize the interaction between p11 and 5-HTR4, demonstrating that (1) p11 and 5-HTR4 mRNA and protein are coexpressed in brain regions that are relevant for major depression, (2) p11 increases 5-HTR4 surface expression and facilitates 5-HTR4 signaling, and (3) p11 is required for the behavioral antidepressant responses to 5-HTR4 stimulation in vivo. The essential role played by p11 in modulating signaling through 5-HT4 as well as 5-HT1B receptors supports the concept that this protein may be a key determinant of vulnerability to depression.

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Section: Discussionmentioning

confidence: 65%

Role of p11 in Cellular and Behavioral Effects of 5-HT4 Receptor Stimulation

Warner-Schmidt¹,

Flajolet²,

Maller³

et al. 2009

J. Neurosci.

155

171

View full text Add to dashboard Cite

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“…In general, a complex link between 5-HT2A and dopamine tone appears to modulate brain activity (Di Pietro and Seamans, 2007;Lieberman et al, 1998). Consistently, 5-HT2A and D2 receptors are both located on prefrontal pyramidal and nonpyramidal neurons (Fink and Gothert, 2007;Goldman-Rakic, 1998, 2000;Seamans and Yang, 2004), and their signaling is also transmitted through the common intraneuronal pathways (Beaulieu, 2012;de Bartolomeis et al, 2013). Overall, these findings suggest that the relationship between D2 and 5-HT2A modulates neuronal function through multiple mechanisms, and that their balanced stimulation is crucial.…”

Section: Introductionmentioning

confidence: 53%

“…Based on this knowledge, a possible interpretation of the results of the present study is that the combined genetic effect of DRD2 and HTR2A affects working memory processing via their modulation of D2 and 5-HT2A signaling on activity of prefrontal pyramidal neurons. For example, a genetically mediated 5-HT2A expression on prefrontal dopaminergic terminals may differentially regulate dopamine release (Fink and Gothert, 2007). Furthermore, 5-HT2A may also be differently expressed on prefrontal pyramidal neurons and interneurons as a function of rs6314 genotype.…”

Section: Discussionmentioning

confidence: 99%

“…In particular, some studies indicate that antagonism on 5-HT2A receptors indirectly increases DA release in the prefrontal cortex (Fink and Gothert, 2007). On the other hand, other studies report that 5-HT2A agonists increase but 5-HT2A antagonists decrease prefrontal dopamine efflux (Bortolozzi et al, 2005;Pehek et al, 2006).…”

Section: Introductionmentioning

confidence: 97%

“…The 5-HT2A receptor interacts with dopamine systems (Di Giovanni et al, 2010;Fink and Gothert, 2007;Lieberman et al, 1998). In particular, some studies indicate that antagonism on 5-HT2A receptors indirectly increases DA release in the prefrontal cortex (Fink and Gothert, 2007).…”

Section: Introductionmentioning

confidence: 99%

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Variation in Dopamine D2 and Serotonin 5-HT2A Receptor Genes is Associated with Working Memory Processing and Response to Treatment with Antipsychotics

Blasi

Selvaggi

Fazio

et al. 2015

Neuropsychopharmacol

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Dopamine D2 and serotonin 5-HT2A receptors contribute to modulate prefrontal cortical physiology and response to treatment with antipsychotics in schizophrenia. Similarly, functional variation in the genes encoding these receptors is also associated with these phenotypes. In particular, the DRD2 rs1076560 T allele predicts a lower ratio of expression of D2 short/long isoforms, suboptimal working memory processing, and better response to antipsychotic treatment compared with the G allele. Furthermore, the HTR2A T allele is associated with lower 5-HT2A expression, impaired working memory processing, and poorer response to antipsychotics compared with the C allele. Here, we investigated in healthy subjects whether these functional polymorphisms have a combined effect on prefrontal cortical physiology and related cognitive behavior linked to schizophrenia as well as on response to treatment with secondgeneration antipsychotics in patients with schizophrenia. In a total sample of 620 healthy subjects, we found that subjects with the rs1076560 T and rs6314 T alleles have greater fMRI prefrontal activity during working memory. Similar results were obtained within the attentional domain. Also, the concomitant presence of the rs1076560 T/rs6314 T alleles also predicted lower behavioral accuracy during working memory. Moreover, we found that rs1076560 T carrier/rs6314 CC individuals had better responses to antipsychotic treatment in two independent samples of patients with schizophrenia (n ¼ 63 and n ¼ 54, respectively), consistent with the previously reported separate effects of these genotypes. These results indicate that DRD2 and HTR2A genetic variants together modulate physiological prefrontal efficiency during working memory and also modulate the response to antipsychotics. Therefore, these results suggest that further exploration is needed to better understand the clinical consequences of these genotype-phenotype relationships.

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