Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.3.1.28 (chloramphenicol acetyltransferase)
 5,100 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hypophyseal portal dopamine is a major negative regulator of pituitary prolactin (PRL) production. Dopamine has been reported to repress PRL gene transcription in pituitary cells. To facilitate further study of the effect of dopamine on PRL gene activation, we introduced PRL promoter and D2 receptor (D2R) constructs into GH3 cells. Since two D2R isoforms (termed D2S and D2L) have been cloned previously, we first determined which isoform(s) is present in the lactotroph by measuring the level of each mRNA species in rat prolactinoma. mRNA for each D2R isoform was found to be present, with the D2L mRNA in great (c. 6-fold) excess. Because the lactotroph contains both isoforms, the effect of each on the PRL promoter was investigated. The cDNA for each receptor isoform was synthesized by polymerase chain reaction, and cloned into an RSV-based expression vector. GH3 cells were then transiently co-transfected with either of the resulting RSV-D2R constructs plus a PRL-chloramphenicol acetyltransferase (CAT) construct containing the first 1957 base-pairs of PRL gene 5'-flanking DNA. The cells were then incubated 48 h plus or minus the dopamine agonist ergocryptine (ECR). In the presence of either RSV-D2R isoform, ECR yielded a 4-5-fold decrease in CAT activity, an effect not seen in the absence of the RSV-D2R. The promoter specificity of this effect was demonstrated by the inability of ECR to regulate expression of a control RSV-CAT construct. The PRL promoter repression mediated by each receptor isoform had appropriate pharmacology: the specific D2R agonist, quinpirole, yielded results similar to ECR, and the ECR repression was reversed by the dopamine antagonist spiperone.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Either isoform of the dopamine D2 receptor can mediate dopaminergic repression of the rat prolactin promoter. 183 94

Dopamine receptors are involved in many aspects of dopaminergic neurotransmission including regulation of motor control, cognition, affect and neuroendocrine function. The D1A receptor is the most widely distributed dopamine receptor in the brain and is expressed at high levels in the striatum and nucleus accumbens, but is also found throughout cortical, limbic, hypothalamic and thalamic brain regions. We have cloned a 6.4 kb fragment 5' of the human D1A dopamine receptor gene and shown that this region activates transcription of the chloramphenicol acetyltransferase (CAT) gene in a cell-specific manner. To study the expression of these sequences in vivo we analyzed the expression of the E. coli lac Z gene under the regulation of the 6.4 kb fragment in transgenic mice. Expression of the transgene was primarily detected in the brain, with only low levels detected in peripheral tissues. The 5' flanking sequences were able to direct the tissue-specific expression of lac Z in three different lines of transgenic mice, to a number of brain regions including the caudate-putamen, thalamus, amygdala, cerebral cortex, hippocampus and hypothalamus. Greatest expression of the lac Z gene was detected in areas of the thalamus and amygdaloid complex. In the striatum, beta-galactosidase activity was restricted to neurons within the matrix and was not detected within striosomes. Results of this study demonstrate that the 6.4 kb region upstream of the human D1A receptor gene is sufficient to confer tissue-specific expression in the CNS of transgenic mice. Furthermore, expression of the transgene to neurons within the matrix of the striatum, but not the striosomes suggests that expression of the D1A receptor may be regulated differently within these areas.
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PMID:The human D1A dopamine receptor gene promoter directs expression of a reporter gene to the central nervous system in transgenic mice. 763 83

It has been previously demonstrated that several members of the steroid receptor superfamily may be activated by the neurotransmitter dopamine in the apparent absence of cognate ligand. We have examined wild-type and mutant human estrogen receptors (ERs, [Gly400]ER and [Val400]ER, respectively) for their abilities to activate ER-dependent transcription of a transgene in a ligand-independent manner. In cells expressing the wild-type ER, dopamine was nearly as effective as 17 beta-estradiol at inducing the chloramphenicol acetyltransferase activity of the reporter gene in a dose-dependent manner; simultaneous addition of suboptimal concentrations of 17 beta-estradiol and dopamine stimulated transcription more than either compound alone. Dopamine alone was unable to induce gene expression in cells expressing [Val400]ER mutant receptors, but concomitant treatment with 17 beta-estradiol produced a synergistic increase in transcription, suggesting that the ligand may alter the mutant receptor's conformation such that it can be activated subsequently by a dopaminergic signaling mechanism. In the presence of the antiestrogen ICI 164,384, dopamine-stimulated gene expression was undetectable in cells expressing either form of ER. However, simultaneous treatment of cells expressing wild-type ER with trans-4-hydroxytamoxifen and dopamine resulted in transgene expression that was additive in nature compared to either compound alone; similar treatment of cells expressing [Val400]ER produced a synergistic increase. Our results suggest that ligand and ligand-independent activation of the ER initiate from distinct pathways and that the latter may occur in a variety of target tissues subject to modulation by receptor ligands.
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PMID:Modulation of the ligand-independent activation of the human estrogen receptor by hormone and antihormone. 832 92