Growth hormone secretagogue receptor constitutive activity impairs voltage‐gated calcium channel‐dependent inhibitory neurotransmission in hippocampal neurons

Damonte, Valentina Martínez; Rodríguez, Sergio; Raingo, Jesica

doi:10.1113/jp276256

Cited by 36 publications

(40 citation statements)

References 96 publications

(77 reference statements)

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“…DEGs are enriched in the 13 KEGG pathway, and some of them are related to tissue growth by regulating growth-related hormones ( Table 2). Glutamatergic synapse can develop the growth neurons and promote the construction of cortical networks by affecting the expression of Growth hormone secretagogue receptor (GHSR) [50]. The Thyroid hormone signaling pathway plays a key role in muscle formation and fat metabolism in pigs by regulating thyroid hormones [51].…”

Section: Discussionmentioning

confidence: 99%

Comparative Transcriptomic Analysis of the Pituitary Gland between Cattle Breeds Differing in Growth: Yunling Cattle and Leiqiong Cattle

Arbab

Zhang

et al. 2020

Animals

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The hypothalamic–pituitary–thyroid (HPT) axis hormones regulate the growth and development of ruminants, and the pituitary gland plays a decisive role in this process. In order to identify pivotal genes in the pituitary gland that could affect the growth of cattle by regulating the secretion of hormones, we detected the content of six HPT hormones related to growth in the plasma of two cattle breeds (Yunling and Leiqiong cattle, both also known as the zebu cattle) with great differences in growth and compared the transcriptome data of their pituitary glands. Our study found that the contents of GH, IGF, TSH, thyroxine, triiodothyronine, and insulin were significantly different between the two breeds, which was the main cause of the difference in growth; 175 genes were identified as differentially expressed genes (DEGs). Functional association analyses revealed that DEGs were mainly involved in the process of transcription and signal transduction. Combining the enrichment analysis and protein interaction analysis, eight DEGs were predicted to control the growth of cattle by affecting the expression of growth-related hormones in the pituitary gland. In summary, our results suggested that SLC38A1, SLC38A3, DGKH, GNB4, GNAQ, ESR1, NPY, and GAL are candidates in the pituitary gland for regulating the growth of Yunling and Leiqiong cattle by regulating the secretion of growth-related hormones. This study may help researchers further understand the growth mechanisms and improve the artificial selection of zebu cattle.

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Section: Discussionmentioning

confidence: 99%

Comparative Transcriptomic Analysis of the Pituitary Gland between Cattle Breeds Differing in Growth: Yunling Cattle and Leiqiong Cattle

Arbab

Zhang

et al. 2020

Animals

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“…The importance of GPCR agonist independent activity is becoming increasingly clear ( Costa and Cotecchia, 2005 ; Meye et al, 2014 ). For instance, our laboratory has demonstrated that constitutive activity of two different GPCRs has a great impact on calcium channel function ( López Soto et al, 2015 ; Agosti et al, 2017 ; Mustafá et al, 2017 ; Martínez Damonte et al, 2018 ). For D1/D5R, there is an abundance of in vitro reports demonstrating a basal increase in Gs activity in several systems ( Plouffe et al, 2010 ; Zhang et al, 2014 ; Zhang et al, 2015 ).…”

Section: Introductionmentioning

confidence: 99%

Constitutive activity of dopamine receptor type 1 (D1R) increases CaV2.2 currents in PFC neurons

McCarthy

Chou-Freed

Rodríguez

et al. 2020

Journal of General Physiology

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Alterations in dopamine receptor type 1 (D1R) density are associated with cognitive deficits of aging and schizophrenia. In the prefrontal cortex (PFC), D1R plays a critical role in the regulation of working memory, which is impaired in these cognitive deficit states, but the cellular events triggered by changes in D1R expression remain unknown. A previous report demonstrated that interaction between voltage-gated calcium channel type 2.2 (CaV2.2) and D1R stimulates CaV2.2 postsynaptic surface location in medial PFC pyramidal neurons. Here, we show that in addition to the occurrence of the physical receptor-channel interaction, constitutive D1R activity mediates up-regulation of functional CaV2.2 surface density. We performed patch-clamp experiments on transfected HEK293T cells and wild-type C57BL/6 mouse brain slices, as well as imaging experiments and cAMP measurements. We found that D1R coexpression led to ∼60% increase in CaV2.2 currents in HEK293T cells. This effect was occluded by preincubation with a D1/D5R inverse agonist, chlorpromazine, and by replacing D1R with a D1R mutant lacking constitutive activity. Moreover, D1R-induced increase in CaV2.2 currents required basally active Gs protein, as well as D1R-CaV2.2 interaction. In mice, intraperitoneal administration of chlorpromazine reduced native CaV currents’ sensitivity to ω-conotoxin-GVIA and their size by ∼49% in layer V/VI pyramidal neurons from medial PFC, indicating a selective effect on CaV2.2. Additionally, we found that reducing D1/D5R constitutive activity correlates with a decrease in the agonist-induced D1/D5R inhibitory effect on native CaV currents. Our results could be interpreted as a stimulatory effect of D1R constitutive activity on the number of CaV2.2 channels available for dopamine-mediated modulation. Our results contribute to the understanding of the physiological role of D1R constitutive activity and may explain the noncanonical postsynaptic distribution of functional CaV2.2 in PFC neurons.

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“…The G protein-coupled ghrelin receptor is expressed in the pituitary, hypothalamus, hippocampus, vasculature, and GI tract [22]. To investigate if G proteins are required for Rikkunshito-induced depolarization of pacemaker potentials, we used GDP-β-S, which can permanently inactivate G protein binding proteins [23,24].…”

Section: Involvement Of G Proteins In Rikkunshito-induced Depolarizatmentioning

confidence: 99%

Rikkunshito Depolarizes Pacemaker Potentials of Cultured Interstitial Cells of Cajal through Ghrelin Receptors in Murine Small Intestine

et al. 2019

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Background: Rikkunshito has been used to treat gastrointestinal (GI) disorders. The purpose of this study was to investigate the effects of Rikkunshito, a traditional Japanese herbal medicine, on the pacemaker potentials of interstitial cells of Cajal (ICCs) from the small intestines of mice. Methods: We isolated ICCs from the small intestines of mice, and the whole-cell patch-clamp configuration was used to record the pacemaker potentials in cultured ICCs and membrane currents. Results: Rikkunshito depolarized ICC pacemaker potentials in a dose-dependent manner. Pretreatment with GSK1614343 or (D-Lys3)-growth hormone-releasing pep-tide-6 inhibited Rikkunshito-induced depolarization of pacemaker potentials. Intracellular GDP-β-S inhibited Rikkunshito-induced effects. In Ca 2+ -free solution or in the presence of thapsigargin, Rikkunshito did not depolarize pacemaker potentials. Moreover, in the presence of U-73122 or xestospongin C, Rikkunshito-induced effects were inhibited. However, in the presence of staurosporine, Go6976 or Rottlerin, Rikkunshito depolarized pacemaker potentials. Furthermore, Rikkunshito inhibited both transient receptor potentials melastatin 7 (TRPM7) and Ca 2+ -activated Clchannels (ANO1) currents. Conclusion: Rikkunshito depolarized pacemaker potentials of ICCs via ghrelin receptor and G protein through internal or external Ca 2+ -, phospholipase C-, and inositol triphosphate-dependent and protein kinase C-, TRPM7-, and ANO1-independent pathways. The study shows that Rikkunshito may alleviate GI motility disorders through its depolarizing effects on ICCs.

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Growth hormone secretagogue receptor constitutive activity impairs voltage‐gated calcium channel‐dependent inhibitory neurotransmission in hippocampal neurons

Cited by 36 publications

References 96 publications

Comparative Transcriptomic Analysis of the Pituitary Gland between Cattle Breeds Differing in Growth: Yunling Cattle and Leiqiong Cattle

Comparative Transcriptomic Analysis of the Pituitary Gland between Cattle Breeds Differing in Growth: Yunling Cattle and Leiqiong Cattle

Constitutive activity of dopamine receptor type 1 (D1R) increases CaV2.2 currents in PFC neurons

Rikkunshito Depolarizes Pacemaker Potentials of Cultured Interstitial Cells of Cajal through Ghrelin Receptors in Murine Small Intestine

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