Identification of membrane-type receptor for bile acids (M-BAR)

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Abstract

Bile acids play an essential role in the solubilization and absorption of dietary fat and lipid-soluble vitamins. Bile acids also modulate the transcription of various genes for enzymes and transport proteins for their own and cholesterol homeostasis through binding to nuclear receptors. Here we report a novel category of bile acid receptor, a membrane-type G protein-coupled receptor (GPCR), BG37. Bile acids induced rapid and dose-dependent elevation of intracellular cAMP levels in BG37-expressing cells, but not in mock-transfected cells, independently of nuclear receptor expression. The rank order of potency of various bile acids for BG37-expressing cells was different from that for the nuclear receptor-mediated response. These observations demonstrate the presence of two independent signaling pathways for bile acids; membrane-type GPCR for rapid signaling and nuclear receptors for delayed signaling. Expression of BG37 was detected in various specific tissues, suggesting its physiological role, although it remains to be further characterized.

Section snippets

Materials and methods

Cloning of human BG37. Putative 5 and 3 ends of BG37 ORF were identified by RACE method using human fetus Marathon-Ready cDNA (Clontech). Using primers, 5-CCCCTGTCCCCAGGACCAAGATG-3 and 5-TTAGTTCAAGTCC-AGGTCGACACTGCTTT-3, determined from the RACE products, hBG37 ORF was amplified. PCR conditions were 94 °C for 9 min, followed by 26 cycles of 94 °C for 30 s, 68 °C for 3 min, and finally 94°C for 30 s, then 62 °C for 8 min. The ORFs of mouse and rat BG37 were similarly identified.

Cell culture.

Results and discussion

In a search of the GenBank DNA database with amino acid sequences of known GPCRs, we found a novel human GPCR, human BG37 (hBG37). The putative coding sequence of hBG37 cloned by PCR is 993 bp and encodes 330 amino acids constituting seven transmembrane domains, which is characteristic of GPCRs (Fig. 1). It showed 28% identity to human EDG-1 (sphingosine-1-phosphate receptor), a member of the class 1 (rhodopsin-like) GPCR superfamily. Mouse and rat BG37 cDNAs were also identified, showing high

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