Functional ATP receptors  in rat anterior pituitary cells

Villalobos, Carlos; Alonso-Torre, Sara R.; Núñez, Lucı́a; García‐Sancho, Javier

doi:10.1152/ajpcell.1997.273.6.c1963

Cited by 34 publications

(34 citation statements)

References 28 publications

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“…This is consistent with the notion that binding of growth hormone-releasing hormone to its receptor activates not only the stimulatory subunit a of the G-protein (Ga-S, cAMP-dependent pathways) but also Ga-I, Gb, and Gg, leading to release of intracellular free Ca 2C , which then further triggers secretion of GH (44,45). Moreover, ATP, which is co-released with pituitary hormones, induces an increase in free Ca 2C in pituitary cells (46). These data strongly suggest that dysregulation of the calcium signaling might be an important co-signal in somatotrophs and potentially involved in pituitary tumorigenesis.…”

Section: Discussionmentioning

confidence: 99%

Landscape of somatic mutations in sporadic GH-secreting pituitary adenomas

Ronchi¹,

Peverelli

Herterich

et al. 2016

European Journal of Endocrinology

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Context: Alterations in the cAMP signaling pathway are common in hormonally active endocrine tumors. Somatic mutations at GNAS are causative in 30-40% of GH-secreting adenomas. Recently, mutations affecting the USP8 and PRKACA gene have been reported in ACTH-secreting pituitary adenomas and cortisol-secreting adrenocortical adenomas respectively. However, the pathogenesis of many GH-secreting adenomas remains unclear. Aim: Comprehensive genetic characterization of sporadic GH-secreting adenomas and identification of new driver mutations. Design: Screening for somatic mutations was performed in 67 GH-secreting adenomas by targeted sequencing for GNAS, PRKACA, and USP8 mutations (nZ31) and next-generation exome sequencing (nZ36). Results: By targeted sequencing, known activating mutations in GNAS were detected in five cases (16.1%), while no somatic mutations were observed in both PRKACA and USP8. Whole-exome sequencing identified 132 protein-altering somatic mutations in 31/36 tumors with a median of three mutations per sample (range: 1-13). The only recurrent mutations have been observed in GNAS (31.4% of cases). However, seven genes involved in cAMP signaling pathway were affected in 14 of 36 samples and eight samples harbored variants in genes involved in the calcium signaling or metabolism. At the enrichment analysis, several altered genes resulted to be associated with developmental processes. No significant correlation between genetic alterations and the clinical data was observed. Conclusion: This study provides a comprehensive analysis of somatic mutations in a large series of GH-secreting adenomas. No novel recurrent genetic alterations have been observed, but the data suggest that beside cAMP pathway, calcium signaling might be involved in the pathogenesis of these tumors.

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Section: Discussionmentioning

confidence: 99%

Landscape of somatic mutations in sporadic GH-secreting pituitary adenomas

Ronchi¹,

Peverelli

Herterich

et al. 2016

European Journal of Endocrinology

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“…Using the technique of single-cell calcium measurement, the initial characterization of purinoceptors in anterior pituitary cells were identified [2][3][4][5][6]. These experiments revealed that functional P2X receptors are operative in all secretory cell types.…”

Section: Introductionmentioning

confidence: 99%

Expression of P2Y receptors in the rat anterior pituitary

Guo

Song

et al. 2011

Purinergic Signalling

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In this study, the distribution patterns of P2Y 1 , P2Y 2 P2Y 4 , P2Y 6 , P2Y 12 , and P2Y 13 receptors in the anterior pituitary cells of rat were studied with doublelabeling immunofluorescence and Western blot. The results showed that P2Y receptors were widely expressed in the anterior pituitary. P2Y 1 and P2Y 4 receptors were found to be expressed in the majority of gonadotrophs and thyrotrophs, P2Y 2 receptors were expressed in a small subpopulation of lactotrophs and almost all the folliculo-stellate cells, that were also stained with S100 protein immunoreactivity. P2Y 6 receptors were expressed in macrophages. P2Y 13 receptors were expressed in a small subpopulation of cells in the rat anterior pituitary, the identity of which needs to be clarified. P2Y 1 and P2Y 4 receptors are co-expressed in some gonadotrophs and thyrotrophs. Corticotrophs and somatotrophs were found not to express P2Y receptors in this study. FSH and TSH were shown to coexist in the same endocrine cells in rat anterior pituitary. The present data suggests that purines and/or pyrimidines could be involved in regulating the functions of gonadotrophs and thyrotrophs via P2Y 1 and P2Y 4 receptors, some lactotrophs via P2Y 2 receptors, and folliculo-stellate cells via P2Y 2 receptors in the rat anterior pituitary.

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“…Molecular cloning and functional characterization of rat P2YRs in the pituitary revealed the expression of P2Y 2 R with the pharmacological profile resembling the one observed in sheep pituitary cells (15). More recent studies have also suggested the presence of P2XRs in normal and immortalized pituitary cells (4,16,17). Initially, the mRNA messages for P2X 2a R and its spliced form, P2X 2b R, were identified in pituitary cells (18 -20).…”

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confidence: 96%

Role of Nucleotide P2 Receptors in Calcium Signaling and Prolactin Release in Pituitary Lactotrophs

González-Iglesias

Stojilković

2003

Journal of Biological Chemistry

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Anterior pituitary cells express nucleotide-gated G protein-coupled P2 receptors (P2YRs) and cation-conducting channels (P2XRs). However, the identification of P2 receptors subtypes and their native ligands, and the distribution and function of these receptors within the secretory and non-secretory pituitary cells has been incompletely characterized. The focus in this study was on lactotroph subpopulation of cells. ATP and ADP, but not UTP and UDP, triggered calcium signaling in a majority (85%) of lactotrophs and prolactin release in mixed pituitary cells. Consistent with the role of P2 receptors in signaling and secretion, the actions of ATP and ADP were abolished in the presence of apyrase, an ectonucleotidase. Transcripts for G q -coupled calciummobilizing P2Y 1 R, P2Y 2 R, P2Y 4 R, and P2Y 6 R, as well as G i -coupled P2Y 12 R, were identified in mixed anterior pituitary cells. The ligand-selectivity profile of calcium mobilization-dependent signaling and prolactin secretion and the blockade of these responses by pyridoxal 5-phosphate 6-azophenyl-2,4-disulphonic acid indicated that P2Y 1 R mediates the stimulatory action of ATP and ADP. Within the channels expressed in anterior pituitary (P2X 2 R, P2X 3 R, P2X 4 R, and P2X 7 R), the P2X 4 R subtype provides a major pathway for calcium influx-dependent signaling and prolactin secretion. This conclusion was based on comparison of native to recombinant channels with respect to their ligand preference, sensitivity to pyridoxal 5-phosphate 6-azophenyl-2,4-disulphonic acid, and the rates of calcium signal desensitization.Purines (adenosine, ADP, and ATP) and pyrimidines (UDP and UTP) are not only important intracellular molecules, but also function as extracellular messengers by activating distinct plasma membrane receptors. These receptors were termed "purinergic" in the seventies and belong to two groups: P1 receptors (P1Rs) 1 that are activated by adenosine and P2 receptors (P2Rs) that recognize mainly ADP, ATP, UDP, and UTP. Four subtypes comprise the P1R family of G protein-coupled receptors, termed A 1 , A 2A , A 2B , and A 3 , whereas P2Rs are composed of two families: the ligand-gated channels (P2XR) and the G protein-coupled receptors (P2YR). To date, seven functional channels (P2X 1 to P2X 7 ) and six receptors (P2Y 1 , P2Y 2 , P2Y 4 , P2Y 6 , P2Y 11 , and P2Y 12 ) have been identified in mammals (1-3). P2Rs are expressed in a variety of non-excitable and excitable tissues. Three lines of previously published evidence also indicate that an extracellular nucleotide-controlled signaling system is expressed and operative in anterior pituitary cells. First, ATP is co-stored with hormones in secretory vesicles and co-secreted by anterior pituitary cells (4, 5). Second, P1Rs, P2YRs, and P2XRs are expressed in these cells and their activation leads to amplification of calcium signals and secretion triggered by hypothalamic neurohormones (6 -8). Third, the autocrine/paracrine actions of ATP are controlled by ectonucleotidases (4). These enzymes degrade extracel...

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Functional ATP receptors in rat anterior pituitary cells

Cited by 34 publications

References 28 publications

Landscape of somatic mutations in sporadic GH-secreting pituitary adenomas

Landscape of somatic mutations in sporadic GH-secreting pituitary adenomas

Expression of P2Y receptors in the rat anterior pituitary

Role of Nucleotide P2 Receptors in Calcium Signaling and Prolactin Release in Pituitary Lactotrophs

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