Rat TRH receptor type 2 exhibits higher basal signaling activity than TRH receptor type 1.
Two types of rat TRH receptor (TRH-R1 and TRH-R2) have been identified and shown previously to exhibit similar binding and stimulated signaling activity via the phosphoinositide-calcium transduction pathway. Since mouse TRH-R1 exhibits basal (or constitutive or ligand-independent) signaling activity, we compared basal signaling by TRH-R1 and TRH-R2. Basal signaling was measured as receptor-mediated reporter gene induction via different transcription factors. We found that TRH-R2 exhibited higher basal signaling activity than TRH-R1 via pathways mediated by transcription factors AP-1, Elk-1 and CREB. Furthermore, CREB-mediated transcription was directly dependent on the level of TRH-R2 expression and was inhibited by midazolam, a specific inverse agonist of basal TRH-R signaling. Since TRH-R1 and TRH-R2 exhibit distinct anatomic distributions in the rat, it is possible that TRH ligand-independent signaling is more important in tissues/cells in which TRH-R2 is expressed and less important in tissues in which TRH-R1 is found.
Wang
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Department of Medicine, Weill Medical College of Cornell University, New York, NY 10021-4896, USA.
Gershengorn
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D000818:Animals; D022762:CCAAT-Enhancer-Binding Proteins; D017362:Cyclic AMP Response Element-Binding Protein / Q000502:physiology; D004268:DNA-Binding Proteins / Q000502:physiology; D005786:Gene Expression Regulation / Q000502:physiology; D017930:Genes, Reporter / Q000235:genetics; D006801:Humans; D008156:Luciferases / Q000235:genetics; D008874:Midazolam / Q000494:pharmacology; D020033:Protein Isoforms / Q000502:physiology*; D011518:Proto-Oncogene Proteins / Q000502:physiology; D051381:Rats; D018025:Receptors, Thyrotropin-Releasing Hormone / Q000819:agonists / Q000502:physiology*; D015398:Signal Transduction; D018808:Transcription Factor AP-1 / Q000502:physiology; D051742:Transcription Factor CHOP; D014157:Transcription Factors / Q000502:physiology; D014158:Transcription, Genetic / Q000187:drug effects; D015533:Transcriptional Activation; D050807:ets-Domain Protein Elk-1
D022762:CCAAT-Enhancer-Binding Proteins; D017362:Cyclic AMP Response Element-Binding Protein; C497249:DDIT3 protein, human; D004268:DNA-Binding Proteins; C497251:Ddit3 protein, rat; C494112:ELK1 protein, human; C494114:Elk1 protein, rat; D020033:Protein Isoforms; D011518:Proto-Oncogene Proteins; D018025:Receptors, Thyrotropin-Releasing Hormone; D018808:Transcription Factor AP-1; D014157:Transcription Factors; D050807:ets-Domain Protein Elk-1; D051742:Transcription Factor CHOP; D008156:Luciferases; D008874:Midazolam