Adenosine signalling pathways in the pituitary gland: one ligand, multiple receptors

Rees, D. A.; Scanlon, M. F.; Ham, Jack

doi:10.1677/joe.0.1770357

Cited by 28 publications

(23 citation statements)

References 43 publications

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“…The hypothalamic-pituitary-adrenal axis plays a key role in regulation of endocrine and immune responses, in which the local concentration of adenosine in the pituitary may be of paramount importance (Rees et al, 2003). The present study provides the first evidence that various nucleoside transporters are expressed in pituitary.…”

Section: Lu Et Almentioning

confidence: 57%

Tissue Distribution of Concentrative and Equilibrative Nucleoside Transporters in Male and Female Rats and Mice

Chen²,

2004

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ABSTRACT:Concentrative nucleoside transporters (Cnts) and equilibrative nucleoside transporters (Ents) have essential physiological functions and are important in disposition of anticancer and antiviral nucleoside analogs. Information on tissue distribution of Cnts and Ents in rodents is sparse. Thus, the present study aimed to determine the distribution of Cnt1-3 and Ent1-3 transcripts in 19 tissues of Sprague-Dawley rats and C57BL/6 mice of both genders. These six transcripts were quantified using the branched DNA signal amplification assay. Cnt1 transcripts were highest in small intestine, followed by kidney and testes, with similar expression in both species. Cnt2 mRNA was expressed highest in the small intestine of both rats and mice, intermediate in liver of rats but not in mice, and lower in thymus and spleen of both species. Cnt3 mRNA has marked species differences, with the highest expression in lung of rats but uterus of mice. Ent1 mRNA was most highly expressed in testes and lung of both species. Ent1 mRNA was highly expressed in liver and pituitary of mice, but not in rats. Ent2 mRNA was highly expressed in testes and brain of both species. Ent3 mRNA was highest in kidney, followed by testes, in both species. Significant gender differences were observed in kidney (mouse) and heart (rat). These studies demonstrate that in general, tissue distribution of Cnt and Ent is similar in rats and mice. However, a few important species and gender differences do exist, which could be responsible for related differences in efficacy and toxicity of substrates for these transporters.

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Section: Lu Et Almentioning

confidence: 57%

Tissue Distribution of Concentrative and Equilibrative Nucleoside Transporters in Male and Female Rats and Mice

Chen²,

2004

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“…This indicated the presence of A2 receptors and subsequent studies also showed the existence of A1 receptors that are coupled to adenylate cyclase and phospholipase C in several pituitary cell lines [105][106][107][108][109]. More detailed experiments using several complementary methods showed that adenosine receptors are differentially expressed in the different cell types within the anterior pituitary gland [110][111][112]. There are essentially two types of cells in the anterior pitui- tary gland; those that classically secrete pituitary hormones and those that do not.…”

Section: Anterior Pituitary Glandmentioning

confidence: 88%

The Adenosine A2b Receptor: Its Role in Inflammation

Ham¹,

Rees²

2008

EMIDDT

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Investigations into the role of the adenosine A2b receptor have been enigmatic due to the lack of good selective high affinity agonists and antagonists. Over the last few years several new antagonist compounds, based either on a xanthine or pyrrolpyrimidine (polyheterocyclic) structure have been designed and these have been used to localise A2b receptors in different tissues and to determine their function. Recently, animals harbouring either a loss or an over-expression of the A2b receptor have been created and these suggest an anti-inflammatory role for the receptor. In this short review, we describe how the A2b receptor influences inflammation in different tissues. In the anterior pituitary gland the A2b receptors exist predominantly in folliculostellate cells where it stimulates secretion of IL-6 and VEGF and influences gap-junctional communication via connexin-43. The A2b receptor also mediates the release of pro-inflammatory cytokines from many tissues such as bronchial smooth muscle, intestinal epithelial cells and mast cells. The presence of a HIF-1alpha binding site in the promoter region of the A2b receptor gene shows that it is strongly implicated in hypoxia and angiogenesis. Targeting the A2b receptor may also be useful in combating autoimmune type I diabetes. These findings, together, indicate that the A2b receptor plays a role in inflammation; its precise action, whether pro- or anti-inflammatory however may be cell type dependent. Nevertheless several A2b receptor antagonists are being developed for therapeutic intervention and these are either at the preclinical stage or in phase I clinical trials as is the case for CVT-6883 for asthma.

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“…Earlier studies also have revealed that TRH-responsive cells and PRL-secreting GH 3 immortalized pituitary cells express the G q/11 -coupled P2Y 1 Rs, leading to the activation of phospholipase C and generation of InsP 3 and diacylglycerol (13), as well as A 1 Rs that signal through G i/o heterotrimeric proteins (28,33). In the hypothalamopituitary system, the expression of P2Y 1 R, P2X 4 R, and/or A 1 R is also observed in other cell types.…”

Section: Discussionmentioning

confidence: 99%

“…Chen et al (6) cloned the UTPactivated P2Y 2 R from a rat pituitary complementary DNA library (6), and our recent studies (13) have shown the expression of a Ca 2ϩ -mobilizing P2Y 1 R that can be activated by ATP and ADP, but not UTP, in lactotrophs and other unidentified pituitary cells. Anterior pituitary cells express three subtypes of adenosine receptors, A 1 R, A 2A R, and A 2B R, and activation of these receptors leads to modulation of Ca 2ϩ influx through Ca v channels (27,33,34).…”

mentioning

confidence: 99%

Characterization of purinergic P2X₄receptor channels expressed in anterior pituitary cells

Zemková

Kučka

et al. 2010

American Journal of Physiology-Endocrinology and Metabolism

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Anterior pituitary cells express cation-conducting P2X receptor channels (P2XRs), but their molecular identity, electrophysiological properties, cell-specific expression pattern, and physiological roles have been only partially characterized. In this study, we show by quantitative RT-PCR that mRNA transcripts for the P2X4 subunit are the most abundant in rat anterior pituitary tissue and confirm the P2X4R protein expression by Western blot analysis. Single-cell patch-clamp recordings show that extracellular ATP induced an inward depolarizing current in a majority of thyrotropin-releasing hormone-responsive pituitary cells, which resembled the current profile generated by recombinant P2X4R. The channels were activated and desensitized in a dose-dependent manner and deactivated rapidly. Activation of these channels led to stimulation of electrical activity and promotion of voltage-gated and voltageinsensitive Ca 2ϩ influx. In the presence of ivermectin, a specific allosteric modulator of P2X4Rs, there was an approximately fourfold increase in the maximum amplitude of the ATP-induced inward current, accompanied by an increase in the sensitivity of receptors for ATP, slowed deactivation of receptors, and enhanced ATP-induced prolactin release. These results indicate that thyrotropin-releasing hormone-responsive cells, including lactotrophs, express homomeric and/or heteromeric P2X4Rs, which facilitate Ca 2ϩ influx and hormone secretion. adenosine 5=-triphosphatase; adenosine 5=-triphosphatase-gated receptor channels; calcium; lactotrophs; prolactin; ivermectin IN ADDITION TO ITS INTRACELLULAR FUNCTIONS, ATP can be released by excitable and nonexcitable cells and act as an extracellular messenger through the stimulation of P2Y receptors (P2YRs) and P2X receptors (P2XRs). To date, eight mammalian P2YRs have been identified and are denoted as

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Adenosine signalling pathways in the pituitary gland: one ligand, multiple receptors

Cited by 28 publications

References 43 publications

Tissue Distribution of Concentrative and Equilibrative Nucleoside Transporters in Male and Female Rats and Mice

Tissue Distribution of Concentrative and Equilibrative Nucleoside Transporters in Male and Female Rats and Mice

The Adenosine A2b Receptor: Its Role in Inflammation

Characterization of purinergic P2X₄receptor channels expressed in anterior pituitary cells

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Adenosine signalling pathways in the pituitary gland: one ligand, multiple receptors

Cited by 28 publications

References 43 publications

Tissue Distribution of Concentrative and Equilibrative Nucleoside Transporters in Male and Female Rats and Mice

Tissue Distribution of Concentrative and Equilibrative Nucleoside Transporters in Male and Female Rats and Mice

The Adenosine A2b Receptor: Its Role in Inflammation

Characterization of purinergic P2X4receptor channels expressed in anterior pituitary cells

Contact Info

Product

Resources

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Characterization of purinergic P2X₄receptor channels expressed in anterior pituitary cells