scholarly journals Differential Expression of Melatonin Receptor Subtypes MelIa, MelIb and MelIc in Relation to Melatonin Binding in the Male Songbird Brain

2014 ◽  
Vol 85 (1) ◽  
pp. 4-14 ◽  
Author(s):  
Leonida Fusani ◽  
Manfred Gahr
Keyword(s):  
Expression Patterns ◽  
General Pattern ◽  
Passerine Bird ◽  
Brain Regions ◽  
Receptor Expression ◽  
Receptor Subtype ◽  
Receptor Subtypes ◽  
Melatonin Receptor ◽  
Brain Areas ◽  
Specific Expression

Previous autoradiography studies illustrated that several areas of the avian brain can bind the pineal hormone melatonin. In birds, there are three melatonin receptor (MelR) subtypes: MelIa, MelIb and MelIc. To date, their brain distribution has not been studied in any passerine bird. Therefore, we investigated mRNA distribution of MelR subtypes in adjacent sections of the brain of two songbirds, the blackcap and the zebra finch, in parallel with that of 2-[125I]-iodomelatonin (IMEL) binding sites in the same brains. The general pattern of receptor expression shown by in situ hybridization of species-specific probes matched well with that of IMEL binding. However, the expression of the three subtypes was area specific with similar patterns in the two species. Some brain areas expressed only one receptor subtype, most brain regions co-expressed either MelIa with MelIb or MelIa with MelIc, whereas few areas expressed MelIb and MelIc or all three receptor subtypes. Since many sensory areas, most thalamic areas and subareas of the neopallium, a cortex analogue, express MelR, it is likely that most sensory motor integration functions are melatonin sensitive. Further, the area-specific expression patterns suggest that the regulatory role of melatonin differs among different brain areas. Since subareas of well-defined neural circuits, such as the visual system or the song control system, are equipped with different receptor types, we hypothesize a diversity of functions for melatonin in the control of sensory integration and behavior.

scholarly journals Comparative analysis of the pituitary and ovarian GnRH systems in the leopard gecko: signaling crosstalk between multiple receptor subtypes in ovarian follicles

2007 ◽  
Vol 38 (2) ◽  
pp. 289-304 ◽  
Author(s):  
Tadahiro Ikemoto ◽  
Min Kyun Park
Keyword(s):  
Pituitary Gland ◽  
Anterior Pituitary ◽  
Expression Patterns ◽  
Ovarian Follicles ◽  
Anterior Pituitary Gland ◽  
Receptor Expression ◽  
Receptor Subtype ◽  
Receptor Subtypes ◽  
Leopard Gecko ◽  
Multiple Receptor

GnRH regulates reproductive functions through interaction with its pituitary receptor in vertebrates. The present study demonstrated that the leopard gecko possessed two and three genes for GnRH ligands and receptors, respectively, though one of the three receptor subtypes had long been thought not to exist in reptiles. Each receptor subtype showed a distinct pharmacology. All types of ligands and receptors showed different expression patterns, and were widely expressed both inside and outside the brain. This report also shows a comparison of the pituitary and ovarian GnRH systems in the leopard gecko during and after the egg-laying season. All three receptor subtypes were expressed in both the whole pituitary and ovary; however, only one receptor subtype could be detected in the anterior pituitary gland. In situ hybridization showed spatial expression patterns of ovarian receptors, and suggested co-expression of multiple receptor subtypes in granulosa cells of larger follicles. Co-transfection of receptor subtypes showed a distinct pharmacology in COS-7 cells compared with those of single transfections. These results suggest that distinct signaling mechanisms are involved in the pituitary and ovarian GnRH systems. Seasonal and developmental variations in receptor expression in the anterior pituitary gland and ovarian follicles may contribute to the seasonal breeding of this animal.

scholarly journals Characterisation of the Contribution of the GABA-Benzodiazepine α1 Receptor Subtype to [11C]Ro15-4513 PET Images

2012 ◽  
Vol 32 (4) ◽  
pp. 731-744 ◽  
Author(s):  
James FM Myers ◽  
Lula Rosso ◽  
Ben J Watson ◽  
Sue J Wilson ◽  
Nicola J Kalk ◽  
...  
Keyword(s):  
Spectral Analysis ◽  
A Priori ◽  
Benzodiazepine Receptor ◽  
Brain Regions ◽  
Complex Model ◽  
Receptor Subtype ◽  
Receptor Subtypes ◽  
Time Activity ◽  
Positron Emission ◽  
The Impact

This positron emission tomography (PET) study aimed to further define selectivity of [11C]Ro15-4513 binding to the GABARα5 relative to the GABARα1 benzodiazepine receptor subtype. The impact of zolpidem, a GABARα1-selective agonist, on [11C]Ro15-4513, which shows selectivity for GABARα5, and the nonselective benzodiazepine ligand [11C]flumazenil binding was assessed in humans. Compartmental modelling of the kinetics of [11C]Ro15-4513 time-activity curves was used to describe distribution volume ( VT) differences in regions populated by different GABA receptor subtypes. Those with low α5 were best fitted by one-tissue compartment models; and those with high α5 required a more complex model. The heterogeneity between brain regions suggested spectral analysis as a more appropriate method to quantify binding as it does not a priori specify compartments. Spectral analysis revealed that Zolpidem caused a significant VT decrease (~10%) in [11C]flumazenil, but no decrease in [11C]Ro15-4513 binding. Further analysis of [11C]Ro15-4513 kinetics revealed additional frequency components present in regions containing both α1 and α5 subtypes compared with those containing only α1. Zolpidem reduced one component (mean ± s.d.: 71% ± 41%), presumed to reflect α1-subtype binding, but not another (13% ± 22%), presumed to reflect α5. The proposed method for [11C]Ro15-4513 analysis may allow more accurate selective binding assays and estimation of drug occupancy for other nonselective ligands.

scholarly journals Regulation of angiotensin II receptors and extracellular matrix turnover in human retinal pigment epithelium: role of angiotensin II

2008 ◽  
Vol 295 (6) ◽  
pp. C1633-C1646 ◽  
Author(s):  
Gary E. Striker ◽  
Francoiçe Praddaude ◽  
Oscar Alcazar ◽  
Scott W. Cousins ◽  
Maria E. Marin-Castaño
Keyword(s):  
Extracellular Matrix ◽  
Angiotensin Ii ◽  
Type Iv Collagen ◽  
Pigment Epithelium ◽  
Receptor Expression ◽  
Age Related Macular Degeneration ◽  
Receptor Subtype ◽  
Receptor Subtypes ◽  
Ang Ii ◽  
Type Iv

The early stage of age-related macular degeneration (AMD) is characterized by the formation of subretinal pigment epithelium (RPE) deposits as a result of the dysregulation in the turnover of extracellular matrix (ECM) molecules. However, the mechanism involved remains unclear. Hypertension (HTN) is an important risk factor for AMD, and angiotensin II (ANG II) is the most important hormone associated with HTN. However, the relevance of ANG II receptors and ANG II effects on RPE have not been investigated yet. Therefore, the expression and regulation of ANG II receptors as well as the ECM turnover were studied in human RPE. ANG II receptors were expressed and upregulated by ANG II in human RPE. This regulation resulted in functional receptor expression, since an increase in intracellular concentration of calcium was observed upon ANG II stimulation. ANG II also increased matrix metalloproteinase (MMP)-2 activity and MMP-14 at the mRNA and protein levels as well as type IV collagen degradation. These ANG II effects were abolished in the presence of the ANG II receptor subtype 1 (AT1) receptor antagonist candesartan. In contrast, ANG II decreased type IV collagen via both AT1 and AT2 receptors, suggesting a synergistic effect of the two receptor subtypes. In conclusion, we have confirmed the presence of ANG II receptors in human RPE and their regulation by ANG II as well as the regulation of ECM molecules via ANG II receptors. Our data support the hypothesis that ANG II may exert biological function in RPE through ANG II receptors and that ANG II may cause dysregulation of molecules that play a major role in the turnover of ECM in RPE basement membrane and Bruch's membrane, suggesting a pathogenic mechanism to explain the link between HTN and AMD.

scholarly journals Estrogen Receptor β: An Overview and Update

2008 ◽  
Vol 6 (1) ◽  
pp. nrs.06003 ◽  
Author(s):  
Chunyan Zhao ◽  
Karin Dahlman-Wright ◽  
Jan-Åke Gustafsson
Keyword(s):  
Estrogen Receptor ◽  
Target Genes ◽  
Expression Patterns ◽  
Estrogen Signaling ◽  
Receptor Subtypes ◽  
Specific Expression ◽  
Microarray Experiments ◽  
Downstream Target ◽  
Animal Disease Models ◽  
Selective Ligands

The discovery of a second estrogen receptor (ER), designated ERβ (NR3A2), has redefined our knowledge about the mechanisms underlying cellular signaling by estrogens and has broad implications for our understanding of regulation of estrogen-responsive tissues. Highly variable and even contrasting effects of estrogens in different tissues seem to be at least partially explained by different estrogen signaling pathways, involving ERα (NR3A1) and/or ERβ. To date, two key conclusions can be drawn from the significant body of work carried out on the specific roles of the two receptor subtypes in diverse estrogen target tissues. First, ERα and ERβ have different biological functions, as indicated by their specific expression patterns and the distinct phenotypes observed in ERα and ERβ knockout (αERKO and βERKO) mice. Second, ERα and ERβ appear to have overlapping but also unique sets of downstream target genes, as judged from a set of microarray experiments. Thus, ERα and ERβ have different transcriptional activities in certain ligand, cell-type, and promoter contexts, which may help to explain some of the major differences in their tissue-specific biological actions. The phenotypes observed for βERKO mice have suggested certain therapeutic areas to be further explored. The development of ERβ-selective ligands active in animal disease models indicates new avenues for clinical exploration. ERβ agonists are being explored and validated as drugs for a growing number of indications. Hopefully, some ERβ targeted drugs will prove to be efficient in enhancing human health.

scholarly journals Targeted Disruption of the Mouse Mel1b Melatonin Receptor

2003 ◽  
Vol 23 (3) ◽  
pp. 1054-1060 ◽  
Author(s):  
Xiaowei Jin ◽  
Charlotte von Gall ◽  
Rick L. Pieschl ◽  
Valentin K. Gribkoff ◽  
Jorg H. Stehle ◽  
...  
Keyword(s):  
Functional Redundancy ◽  
Inhibitory Response ◽  
Receptor Subtype ◽  
Receptor Subtypes ◽  
Melatonin Receptor ◽  
Targeted Disruption ◽  
High Affinity ◽  
C3h Mice ◽  
Element Binding Protein ◽  
Residual Response

ABSTRACT Two high-affinity, G protein-coupled melatonin receptor subtypes have been identified in mammals. Targeted disruption of the Mel1a melatonin receptor prevents some, but not all, responses to the hormone, suggesting functional redundancy among receptor subtypes (Liu et al., Neuron 19:91-102, 1997). In the present work, the mouse Mel1b melatonin receptor cDNA was isolated and characterized, and the gene has been disrupted. The cDNA encodes a receptor with high affinity for melatonin and a pharmacological profile consistent with its assignment as encoding a melatonin receptor. Mice with targeted disruption of the Mel1b receptor have no obvious circadian phenotype. Melatonin suppressed multiunit electrical activity in the suprachiasmatic nucleus (SCN) in Mel1b receptor-deficient mice as effectively as in wild-type controls. The neuropeptide, pituitary adenylyl cyclase activating peptide, increases the level of phosphorylated cyclic AMP response element binding protein (CREB) in SCN slices, and melatonin reduces this effect. The Mel1a receptor subtype mediates this inhibitory response at moderate ligand concentrations (1 nM). A residual response apparent in Mel1a receptor-deficient C3H mice at higher melatonin concentrations (100 nM) is absent in Mel1a-Mel1b double-mutant mice, indicating that the Mel1b receptor mediates this effect of melatonin. These data indicate that there is a limited functional redundancy between the receptor subtypes in the SCN. Mice with targeted disruption of melatonin receptor subtypes will allow molecular dissection of other melatonin receptor-mediated responses.

scholarly journals Overexpression of Gastrin-Releasing Peptide Receptors in Tumor-Associated Blood Vessels of Human Ovarian Neoplasms

2007 ◽  
Vol 29 (5) ◽  
pp. 421-433 ◽  
Author(s):  
Achim Fleischmann ◽  
Beatrice Waser ◽  
Jean Claude Reubi
Keyword(s):  
Ovarian Neoplasms ◽  
Ovarian Tumors ◽  
Receptor Expression ◽  
Receptor Subtype ◽  
Receptor Subtypes ◽  
Peptide Receptors ◽  
Gastrin Releasing Peptide ◽  
Bombesin Receptor ◽  
Grp Receptors ◽  
Grp Receptor

Background: Peptide receptors, overexpressed in specific cancers, represent new diagnostic and therapeutic targets. In this study, receptors for the gastrin-releasing peptide (GRP), and other members of the bombesin-family of peptides, were evaluated in ovarian neoplasms. Methods: 75 primary, secondary and metastatic ovarian tumors were investigated for their bombesin-receptor subtype expression, incidence, localization and density using in vitro autoradiography on tissue sections with the universal radioligand 125I-[D-Tyr6, ß-Ala11, Phe13, Nle14]-bombesin(6-14) and the GRP-receptor subtype-preferring 125I-[Tyr4]-bombesin. Results: GRP-receptors were detected in 42/61 primary ovarian tumors; other bombesin-receptor subtypes (BB1, bb3) were rarely present (3/61). Two different tissue compartments expressed GRP-receptors: the tumoral vasculature was the predominant site of GRP-receptor expression (38/61), whereas neoplastic cells more rarely expressed GRP-receptors (14/61). GRP-receptor positive vessels were present in the various classes of ovarian tumors; generally, malignant tumors had a higher incidence of GRP-receptor positive vessels compared to their benign counterparts. The prevalence of such vessels was particularly high in ovarian carcinomas (16/19) and their metastases (5/5). The GRP-receptors were expressed in high density in the muscular vessel wall. Normal ovary (n=10) lacked GRP-receptors. Conclusions: The large amounts of GRP-receptors in ovarian tumor vessels suggest a role in tumoral vasculature and possibly angiogenesis. Further, these vessels might be targeted in vivo with bombesin analogs for diagnosis or for therapy.

scholarly journals Developmental expression of retinoic acid receptors (RARs)

2009 ◽  
Vol 7 (1) ◽  
pp. nrs.07006 ◽  
Author(s):  
Pascal Dollé
Keyword(s):  
Retinoic Acid ◽  
Receptor Gene ◽  
Expression Patterns ◽  
Dominant Negative ◽  
Receptor Expression ◽  
Retinoic Acid Receptors ◽  
Developmental Expression ◽  
Specific Expression ◽  
Functional Studies ◽  
Organ Systems

Here, I review the developmental expression features of genes encoding the retinoic acid receptors (RARs) and the ‘retinoid X’ or rexinoid receptors (RXRs). The first detailed expression studies were performed in the mouse over two decades ago, following the cloning of the murine Rar genes. These studies revealed complex expression features at all stages of post-implantation development, one receptor gene (Rara) showing widespread expression, the two others (Rarb and Rarg) with highly regionalized and/or cell type-specific expression in both neural and non-neural tissues. Rxr genes also have either widespread (Rxra, Rxrb), or highly-restricted (Rxrg) expression patterns. Studies performed in zebrafish and Xenopus demonstrated expression of Rar and Rxr genes (both maternal and zygotic), at early pre-gastrulation stages. The eventual characterization of specific enzymes involved in the synthesis of retinoic acid (retinol/retinaldehyde dehydrogenases), or the triggering of its catabolism (CYP26 cytochrome P450s), all of them showing differential expression patterns, led to a clearer understanding of the phenomenons regulated by retinoic acid signaling during development. Functional studies involving targeted gene disruptions in the mouse, and additional approaches such as dominant negative receptor expression in other models, have pinpointed the specific, versus partly redundant, roles of the RARs and RXRs in many developing organ systems. These pleiotropic roles are summarized hereafter in relationship to the receptors’ expression patterns.

Effect of COX-2 inhibitor NS-398 on expression of PGE2 receptor subtypes in M-1 mouse CCD cells

2001 ◽  
Vol 281 (1) ◽  
pp. F123-F132 ◽  
Author(s):  
Rania Nasrallah ◽  
Odette Laneuville ◽  
Shawn Ferguson ◽  
Richard L. Hébert
Keyword(s):  
Collecting Duct ◽  
Specific Inhibitor ◽  
Receptor Expression ◽  
Receptor Protein ◽  
Prostaglandin E ◽  
Receptor Subtype ◽  
Receptor Subtypes ◽  
Camp Production ◽  
Protein Levels ◽  
Cox 2

Our present study has investigated the effect of cyclooxygenase-2 (COX-2) inhibition on prostaglandin E2 (PGE2) receptor expression in M-1 cortical collecting duct cells and measured their response to PGE2. Using a semiquantitative titration analysis method, we show that following the addition of the COX-2-specific inhibitor NS-398, E-prostanoid receptor subtype (EP3 and EP4) mRNA expression was found to increase threefold each vs. the vehicle-treated control. We also observed that EP1but not EP2 is expressed in M-1 cells and EP2levels are not induced by NS-398. To determine the status of the PGE2 response on exposure to NS-398, we measured cAMP levels in cells after stimulation with varying concentrations of PGE2, then pretreated the cells with 10 μM NS-398 before PGE2 exposure and found a significant rise in the stimulatory effect of PGE2 on cAMP production. Finally, Western blot analysis of the levels of the EP4 receptor protein in control vs. NS-398-treated cells revealed an induction in protein levels in these cells, correlating with the induction in EP4 mRNA. We conclude that NS-398 upregulates the expression of EP3 and EP4 mRNA in M-1 cells. Also, EP4 protein levels are increased, resulting in an increased stimulation of cAMP production by PGE2.

Influence of moonlight on mRNA expression patterns of melatonin receptor subtypes in the pineal organ of a tropical fish

2014 ◽  
Vol 14 ◽  
pp. 67-70 ◽  
Author(s):  
Yong-Ju Park ◽  
Ji-Gweon Park ◽  
Yuki Takeuchi ◽  
Sung-Pyo Hur ◽  
Young-Don Lee ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Pineal Organ ◽  
Expression Patterns ◽  
Tropical Fish ◽  
Receptor Subtypes ◽  
Melatonin Receptor

Stage-specific expression of P2Y receptors, ecto-apyrase, and ecto-5'-nucleotidase in myeloid leukocytes

1997 ◽  
Vol 273 (3) ◽  
pp. C973-C987 ◽  
Author(s):  
E. E. Clifford ◽  
K. A. Martin ◽  
P. Dalal ◽  
R. Thomas ◽  
G. R. Dubyak
Keyword(s):  
Purinergic Receptor ◽  
Myeloid Cell ◽  
Polymerase Chain Reaction Analysis ◽  
Extracellular Atp ◽  
Receptor Subtype ◽  
Receptor Subtypes ◽  
P2y Receptor ◽  
Specific Expression ◽  
Myeloid Leukocytes ◽  
Myeloid Progenitors

The expression of P2 purinergic receptor subtypes in leukocytes varies with both lineage and developmental stage. Given the recent identification and cloning of at least seven distinct G protein-coupled ATP receptor subtypes (P2Y family), we investigated P2Y receptor subtype expression during myeloid cell differentiation. We observed that KG-1 myeloblasts express P2Y1 but not P2Y2 receptors (previously termed P2U receptors), whereas later myeloid progenitors, including HL-60 promyelocytes and THP-1 monocytes, expressed P2Y2 but not P2Y1 receptors. In KG-1 cells, significant activation of Ca2+ mobilization by P2Y1 receptors was only observed after preincubation with potato apyrase, an exogenous ATPase. This indicated that P2Y1 receptors are desensitized in KG-1 cells by autocrine mechanisms that may involve enhanced release of endogenous nucleotides and/or decreased expression of cell-surface ecto-nucleotidases. We compared the levels of ecto-apyrase activity and expression in KG-1 myeloblasts and HL-60 promyelocytes. Extracellular ATP was rapidly metabolized by HL-60 but not by KG-1 cells. Reverse transcription-polymerase chain reaction analysis indicated that mRNA for CD39 (cluster of differentiation), an identified ecto-apyrase, was present in HL-60 but not KG-1 cells. Ecto-apyrase activity was modestly increased with differentiation of myeloid progenitors with either phorbol 12-myristate 13-acetate (PMA) or dibutyryl adenosine 3',5'-cyclic monophosphate (DBcAMP). Differentiation of HL-60 cells with PMA, but not DBcAMP, strongly induced ecto-5'-nucleotidase activity and CD73 mRNA expression. These observations indicate that signal transduction by extracellular ATP in myeloid leukocytes can be regulated by developmentally programmed changes in the expression of P2Y receptor subtypes and multiple ecto-nucleotidases.

Sign in / Sign up

Export Citation Format

Share Document