Bradykinin receptor B2

Bradykinin receptor B2 is a G-protein coupled receptor for bradykinin, encoded by the BDKRB2 gene in humans.

BDKRB2
Identifiers
AliasesBDKRB2, B2R, BK-2, BK2, BKR2, BRB2, bradykinin receptor B2
External IDsOMIM: 113503; MGI: 102845; HomoloGene: 519; GeneCards: BDKRB2; OMA:BDKRB2 - orthologs
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_000623
NM_001379692

NM_009747

RefSeq (protein)

NP_000614
NP_001366621

NP_033877

Location (UCSC)Chr 14: 96.2 – 96.24 MbChr 12: 105.53 – 105.56 Mb
PubMed search[3][4]
Wikidata
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Mechanism

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The B2 receptor (B2R) is a G protein-coupled receptor, probably coupled to Gq and Gi. A 2022 Nature cryo-EM study of human B2R-Gq complexes by Jinkeng Sheng et al. investigated the proximal activation mechanisms of B2R. Sheng et al. propose that upon B2R binding bradykinin or kallidin to a "bulky orthosteric binding pocket," the phenylalanine F8 or F9 residue of bradykinin or kallidin respectively interacts with a "conserved toggle switch" W283. This hydrophobic interaction facilitates the outward movement of transmembrane domain 6 (TM6) of B2R on the cytoplasmic side of the membrane, as well as outward movement of F279, a key residue within the conserved PIF motif of GPCRs (involving proline, isoleucine and phenylalanine). This rearrangement of the PIF motif disrupts the ionic lock formed by the DRY motif and pushes the NPxxY motif towards the activated state, opening an "intracellular cleft" for insertion of the α5-helix of Gq. [5]

Gq stimulates phospholipase C to increase intracellular free calcium and Gi inhibits adenylate cyclase. Furthermore, the receptor stimulates the mitogen-activated protein kinase pathways. It is ubiquitously and constitutively expressed in healthy tissues.

The B2 receptor forms a complex with angiotensin converting enzyme (ACE), and this is thought to play a role in cross-talk between the renin-angiotensin system (RAS) and the kinin–kallikrein system (KKS). The heptapeptide angiotensin (1-7) also potentiates bradykinin action on B2 receptors.[6]

Kallidin also signals through the B2 receptor. An antagonist for the receptor is Hoe 140 (icatibant).[7]

Function

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The 9 amino acid bradykinin peptide elicits several responses including vasodilation, edema, smooth muscle spasm and nociceptor stimulation.

Gene

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Alternate start codons result in two isoforms of the protein.[8]

See also

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References

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  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000168398Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000021070Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ Shen J, Zhang D, Fu Y, Chen A, Yang X, Zhang H (February 2022). "Cryo-EM structures of human bradykinin receptor-Gq proteins complexes". Nature Communications. 13 (1): 714. Bibcode:2022NatCo..13..714S. doi:10.1038/s41467-022-28399-1. PMC 8821558. PMID 35132089.
  6. ^ Fernandes L, Fortes ZB, Nigro D, Tostes RC, Santos RA, Catelli De Carvalho MH (February 2001). "Potentiation of bradykinin by angiotensin-(1-7) on arterioles of spontaneously hypertensive rats studied in vivo". Hypertension. 37 (2 Pt 2): 703–709. doi:10.1161/01.hyp.37.2.703. PMID 11230360. S2CID 17827058.
  7. ^ Wirth K, Hock FJ, Albus U, Linz W, Alpermann HG, Anagnostopoulos H, et al. (March 1991). "Hoe 140 a new potent and long acting bradykinin-antagonist: in vivo studies". British Journal of Pharmacology. 102 (3): 774–777. doi:10.1111/j.1476-5381.1991.tb12249.x. PMC 1917928. PMID 1364852.{{cite journal}}: CS1 maint: overridden setting (link)
  8. ^ "Entrez Gene: BDKRB2 bradykinin receptor B2".

Further reading

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This article incorporates text from the United States National Library of Medicine, which is in the public domain.