دورية أكاديمية
Long-term agonist exposure induces upregulation of beta 3-adrenergic receptor expression via multiple cAMP response elements.
| العنوان: | Long-term agonist exposure induces upregulation of beta 3-adrenergic receptor expression via multiple cAMP response elements. |
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| المؤلفون: | Thomas RF; Department of Medicine (Pulmonary), Duke University Medical Center, Durham, NC 27710., Holt BD, Schwinn DA, Liggett SB |
| المصدر: | Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 1992 May 15; Vol. 89 (10), pp. 4490-4. |
| نوع المنشور: | Journal Article; Research Support, U.S. Gov't, P.H.S. |
| اللغة: | English |
| بيانات الدورية: | Publisher: National Academy of Sciences Country of Publication: United States NLM ID: 7505876 Publication Model: Print Cited Medium: Print ISSN: 0027-8424 (Print) Linking ISSN: 00278424 NLM ISO Abbreviation: Proc Natl Acad Sci U S A Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Washington, DC : National Academy of Sciences |
| مواضيع طبية MeSH: | Regulatory Sequences, Nucleic Acid*, 1-Methyl-3-isobutylxanthine/*pharmacology , Cyclic AMP/*physiology , Isoproterenol/*pharmacology , Receptors, Adrenergic, beta/*genetics, 3T3 Cells ; Animals ; Base Sequence ; Cell Nucleus/drug effects ; Cell Nucleus/metabolism ; Chloramphenicol O-Acetyltransferase/genetics ; Chloramphenicol O-Acetyltransferase/metabolism ; Gene Expression/drug effects ; Iodocyanopindolol ; Kinetics ; Mice ; Molecular Sequence Data ; Oligodeoxyribonucleotides ; Pindolol/analogs & derivatives ; Pindolol/metabolism ; Polymerase Chain Reaction ; RNA, Messenger/genetics ; RNA, Messenger/metabolism ; Receptors, Adrenergic, beta/metabolism ; Transcription, Genetic/drug effects ; Transfection ; Up-Regulation/drug effects ; Vero Cells |
| مستخلص: | During continuous stimulation by agonist, beta 1- and beta 2-adrenergic receptors (ARs) undergo processes that lead to decreases in receptor expression. This receptor down-regulation serves to limit the cellular cAMP response during chronic agonist exposure. In the recently described third subtype of the beta AR, denoted beta 3AR, we found four potential cAMP response elements in the 5' flanking region, suggesting that expression of this receptor might be positively regulated by agonists. These elements were cloned into the vector pA10CAT2, which contains a chloramphenicol acetyltransferase reporter gene, and transiently expressed in VERO cells. Three of these elements, TGACTCCA, TGAGGTCT, and CGAGGTCA (located 518, 622, and 1125 bases upstream of the beta 3AR coding block, respectively) were found to increase transcription of the chloramphenicol acetyltransferase gene in response to cAMP analogues and agents that increase intracellular cAMP. 3T3-F442A cells, when differentiated into the adipocyte phenotype by insulin, expressed beta 3AR, and nuclear runoff studies from such cells confirmed cAMP enhancement of beta 3AR mRNA transcription. In these cells, beta 3AR mRNA increased in response to exposure to the beta 3AR agonist isoproterenol and remained elevated during exposures of up to 24-30 hr. During prolonged exposure to agonist, no downregulation of beta 3AR expression in 3T3-F442A cells occurred. Indeed, beta 3AR expression increased during agonist exposure to approximately 165% of basal expression. In marked contrast, beta 1AR expression declined by approximately 70% in response to chronic agonist exposure. These studies reveal a subtype-specific prolonged transcriptional regulation of a beta AR gene by the end product of its signal transduction pathway. Thus, the beta 3AR undergoes a paradoxical increase in receptor expression during chronic agonist exposure. |
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| معلومات مُعتمدة: | R01 HL45967 United States HL NHLBI NIH HHS |
| سلسلة جزيئية: | GENBANK M62473 |
| المشرفين على المادة: | 0 (Oligodeoxyribonucleotides) 0 (RNA, Messenger) 0 (Receptors, Adrenergic, beta) 83498-72-0 (Iodocyanopindolol) BJ4HF6IU1D (Pindolol) E0399OZS9N (Cyclic AMP) EC 2.3.1.28 (Chloramphenicol O-Acetyltransferase) L628TT009W (Isoproterenol) TBT296U68M (1-Methyl-3-isobutylxanthine) |
| تواريخ الأحداث: | Date Created: 19920515 Date Completed: 19920616 Latest Revision: 20190501 |
| رمز التحديث: | 20221213 |
| مُعرف محوري في PubMed: | PMC49108 |
| DOI: | 10.1073/pnas.89.10.4490 |
| PMID: | 1374904 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 0027-8424 |
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| DOI: | 10.1073/pnas.89.10.4490 |