Structure and genomic organization of the human B{sub 1} receptor gene for kinins (BDKRB1)
- Universite Laval, Quebec (Canada)
- Merck Research Labs., Rahway, NJ (United States); and others
Two subtypes of mammalian bradykinin receptors, B{sub 1} and B{sub 2} (BDKRB1 and BDKRB2), have been defined based on their pharmacological properties. The B{sub 1} type kinin receptors have weak affinity for intact BK or Lys-BK but strong affinity for kinin metabolites without the C-terminal arginine (e.g., des-Arg{sup 9}-BK and Lys-des-Arg{sup 9}-BK, also called des-Arg{sup 10}-kallidin), which are generated by kininase I. The B{sub 1} receptor expression is up-regulated following tissue injury and inflammation (hyperemia, exudation, hyperalgesia, etc.). In the present study, we have cloned and sequenced the gene encoding human B{sub 1} receptor gene contains three exons separated by two introns. The first and the second exon are noncoding, while the coding region and the 3{prime}-flanking region are located entirely on the third exon. The exon-intron arrangement of the human B{sub 1} receptor gene shows significant similarity with the genes encoding the B{sub 2} receptor subtype in human, mouse, and rat. Sequence analysis of the 5{prime}-flanking region revealed the presence of a consensus TATA box and of numerous candidate transcription factor binding sequences. Primer extension experiments have shown the existence of multiple transcription initiation sites situated downstream and upstream from the consensus TATA box. Genomic Southern blot analysis indicated that the human B{sub 1} receptor is encoded by a single-copy gene. 54 refs., 4 figs.
- OSTI ID:
- 466654
- Journal Information:
- Genomics, Journal Name: Genomics Journal Issue: 3 Vol. 33; ISSN 0888-7543; ISSN GNMCEP
- Country of Publication:
- United States
- Language:
- English
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