Premium
Receptor‐specific crosstalk between prostanoid E receptor 3 and bombesin receptor subtype 3
Author(s) -
Zhang Yan,
Liu Yanfang,
Wu Lehao,
Fan Chao,
Wang Zhiwei,
Zhang Xiuli,
Alachkar Amal,
Liang Xinmiao,
Civelli Olivier
Publication year - 2018
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.201700337rr
Subject(s) - receptor , hek 293 cells , chinese hamster ovary cell , crosstalk , g protein coupled receptor , microbiology and biotechnology , biology , bombesin , chemistry , biochemistry , neuropeptide , physics , optics
Bombesin receptor subtype 3 (BRS‐3) is a GPCR that is expressed in the CNS, peripheral tissues, and tumors. Our understanding of BRS‐3's role in physiology and pathophysiology is limited because its natural ligand is unknown. In an attempt to identify this ligand, we screened toad skin ( Bufo bufo gargarizans Cantor) extracts and identified prostaglandins as putative ligands. In BRS‐3–transfected human embryonic kidney (HEK) cells, we found that prostaglandins, with prostaglandin E2 (PGE2) being the most potent, fulfill the pharmacologic criteria of affinity, selectivity, and specificity to be considered as agonists to the BRS‐3 receptor. However, PGE2 is unable to activate BRS‐3 in different cellular environments. We speculated that EP receptors might be the cause of this cellular selectivity, and we found that EP 3 is the receptor primarily responsible for the differential PGE2 effect. Consequently, we reconstituted the HEK environment in Chinese hamster ovary (CHO) cells and found that BRS‐3 and EP 3 interact to potentiate PGE2 signaling. This potentiating effect is receptor specific, and it occurs only when BRS‐3 is paired to EP 3 . Our study represents an example of functional crosstalk between two distantly related GPCRs and may be of clinical importance for BRS‐3–targeted therapies.—Zhang, Y., Liu, Y., Wu, L., Fan, C., Wang, Z., Zhang, X., Alachkar, A., Liang, X., Civelli, O. Receptor‐specific crosstalk between prostanoid E receptor 3 and bombesin receptor subtype 3. FASEB J. 32, 3184–3192 (2018). www.fasebj.org