Isolation and structural organization of the human preproenkephalin B gene

Horikawa, Saburo; Takai, Toshiyuki; Toyosato, Mitsuyoshi; Takahashi, Hideo; Noda, Masaharu; Kakidani, Hitoshi; Kubo, Tai; Hirose, Tatsuro; Inayama, Seiichi; Hayashida, Hidenori; Miyata, Takashi; Numa, Shosaku

doi:10.1038/306611a0

Cited by 262 publications

(86 citation statements)

References 46 publications

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“…43 Dynorphins bind selectively to the KOR, encoded by OPRK1. [44][45][46] The human PDYN gene contains four exons, covering 15.3 kb on chromosome 20.…”

Section: Introductionmentioning

confidence: 99%

“…A 68-bp repeat variant located about 1.5 kb upstream of the promoter region was identified in the initial sequencing of the gene. 43 The level of gene expression appeared to be affected by the number of copies of the 68-bp repeats. 47,48 Longer alleles appear to increase gene expression while the shorter alleles appear to decrease expression.…”

Section: Introductionmentioning

confidence: 99%

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Association of the κ-opioid system with alcohol dependence

et al. 2006

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Opioid receptors and their endogenous peptide ligands play important roles in the reward and reinforcement of drugs such as heroin, cocaine, and alcohol. The binding of dynorphins to the j-opioid receptor has been shown to produce aversive states, which may prevent the development of reinforcement. We genotyped SNPs throughout OPRK1, encoding the j-opioid receptor, and PDYN, which encodes its ligand prodynorphin, in a group of 1860 European American individuals from 219 multiplex alcohol dependent families. Family-based analyses demonstrated associations between alcohol dependence and multiple SNPs in the promoter and 3 0 end of PDYN, and in intron 2 of OPRK1. Haplotype analyses further supported the association of PDYN. Thus, variations in the genes encoding both the j-opioid receptor and its ligand, OPRK1 and PDYN, are associated with the risk for alcohol dependence; this makes biological sense as variations in either should affect signaling through the j-opioid system.

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“…43 Dynorphins bind selectively to the KOR, encoded by OPRK1. [44][45][46] The human PDYN gene contains four exons, covering 15.3 kb on chromosome 20.…”

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Association of the κ-opioid system with alcohol dependence

et al. 2006

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“…The significance of the existence of these multiple transcriptional start sites and TATA boxes in the human GnRH receptor gene is not known. However, the existence of multiple TATA boxes and transcriptional start sites is not uncommon (38,39). The finding of multiple transcriptional start sites and TATA boxes raises the possibility of tissue-specific regulation and the existence of variable size transcripts.…”

Section: Structure Of the 5 0 Flanking Sequencementioning

confidence: 99%

Molecular structure of the human gonadotropin-releasing hormone receptor gene

Kakar

1997

European Journal of Endocrinology

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GnRH receptors belong to the family of G protein-coupled receptor proteins and have been localized to the anterior pituitary, brain and reproductive organs as well as many steroid-dependent tumor tissues. Recently, cDNAs for the GnRH receptors of several species including the human have been cloned. To determine the structure of the gene encoding the human GnRH receptor, we isolated the receptor gene clones from the human genomic libraries. Comparison of the genomic and cDNA sequences revealed that the human GnRH receptor gene is composed of three exons and two introns and spans over 20 kb in size. Exon 1 encodes the 5 0 untranslated sequence and nucleotide þ 1 to þ 522 in the open reading frame, exon 2 encodes nucleotide þ 523 to þ 742 and exon 3 encodes nucleotide þ 743 to þ 987 in the open reading frame as well as the 3 0 untranslated sequence. Southern blot analysis of genomic DNA and localization of the GnRH receptor gene to a single site on human chromosome 4 (4q13) indicate the presence of a single copy of the gene in the human genome. Several regulatory sequences for various hormones and other regulatory factors were identified, including PEA-3, AP-1, AP-2, and Pit-1 sites. In addition, glucocorticoid/progesterone response element, thyroid hormone response element, and cAMP response element sequences were identified. Reverse transcriptase-primer extension and 5 0 RACE analysis of the human pituitary RNA demonstrated the presence of multiple transcriptional start sites upstream of the translational start site. Analysis of the 5 0 flanking region of the gene also revealed the presence of multiple TATA and CAAT sequences. The finding of multiple transcriptional start sites raises the possibility of tissue-specific regulation and the existence of variable size transcripts. Chimeras containing 1.26 kb (¹534 to 728) of the 5 0 flanking region of the receptor gene and the luciferase (Luc) gene expressed a significant luciferase activity when transfected into a human endometrial tumor cell line (HEC-1A) and a breast tumor cell line (MCF-7) but not in a mouse pituitary gonadotrope cell line (aT3-1), suggesting the existence of multiple promoter elements in the gene. These findings indicate a multiplicity of regulation of expression of the GnRH receptor and provide the substrate for detailed investigation in the reproductive system.

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“…Prodynorphin riboprobes were complementary to a 1.2-kb fragment containing most of exon 4 of the human prodynorphin cDNA (termed preproenkephalin B) 25 in a SP65 vector (courtesy of Dr Jim Douglas) or to a 400-bp (exon 4) subcloned into PGEM vector. The riboprobes were transcribed from their templates using SP6 or T3 polymerase and […”

Section: Riboprobes Preparation and In Situ Hybridizationmentioning

confidence: 99%

Subjects with major depression or bipolar disorder show reduction of prodynorphin mRNA expression in discrete nuclei of the amygdaloid complex

Hurd

2002

Mol Psychiatry

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The dynorphin system has been associated with the regulation of mood. The expression of the prodynorphin mRNA was currently studied in the amygdaloid complex, a brain region critical for emotional processing, in subjects (14-15 per group) diagnosed with major depression, bipolar disorder, or schizophrenia and compared to normal controls. In situ hybridization histochemistry was used to characterize the anatomical distribution and expression levels of the prodynorphin mRNA within the amygdaloid complex. High prodynorphin mRNA levels were expressed in the parvicellular division of the accessory basal, posterior cortical, periamygdaloid cortex, and amygdalohippocampal area in normal subjects. Individuals with major depression had significantly reduced (41-68%) expression of the prodynorphin mRNA in the accessory basal (both parvicellular and magnocellular divisions; P Ͻ 0.01) and amygdalohippocampal area (P Ͻ 0.001) as compared to controls. The bipolar disorder group also showed a significant reduction (37-38%, P Ͻ 0.01) of the mRNA expression levels in the amygdalohippocampal area and in the parvicellular division of the accessory basal. No other amygdala nuclei studied showed any significant differences for the prodynorphin mRNA levels measured in the major depression and bipolar disorder subjects. Additionally, the prodynorphin mRNA expression levels did not differ significantly between the schizophrenic and normal control subjects in any of the amygdala areas examined. These findings indicate specific prodynorphin amygdala impairment in association with mood disorder. Molecular Psychiatry (2002) 7, 75-81.

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Isolation and structural organization of the human preproenkephalin B gene

Cited by 262 publications

References 46 publications

Association of the κ-opioid system with alcohol dependence

Association of the κ-opioid system with alcohol dependence

Molecular structure of the human gonadotropin-releasing hormone receptor gene

Subjects with major depression or bipolar disorder show reduction of prodynorphin mRNA expression in discrete nuclei of the amygdaloid complex

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