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Sökning: onr:"swepub:oai:lup.lub.lu.se:a7701921-8a11-44ef-8322-eccacb1bf1c5" > The sixth transmemb...

  • Leeb, Tosso (författare)

The sixth transmembrane domains of the human B1 and B2 bradykinin receptors are structurally compatible and involved in discriminating between subtype-selective agonists

  • Artikel/kapitelEngelska

Förlag, utgivningsår, omfång ...

  • ASBMB,1997-01-18

Nummerbeteckningar

  • LIBRIS-ID:oai:lup.lub.lu.se:a7701921-8a11-44ef-8322-eccacb1bf1c5
  • https://lup.lub.lu.se/record/a7701921-8a11-44ef-8322-eccacb1bf1c5URI
  • https://doi.org/10.1074/jbc.272.1.311DOI

Kompletterande språkuppgifter

  • Språk:engelska
  • Sammanfattning på:engelska

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  • Ämneskategori:ref swepub-contenttype
  • Ämneskategori:art swepub-publicationtype

Anmärkningar

  • In order to investigate the molecular basis for the ability of the human B1 and B2 bradykinin (BK) receptor subtypes to discriminate between subtype- selective ligands, we constructed chimeric proteins in which the sixth transmembrane domains (TM-VI) of these receptors were exchanged. The pharmacological profiles of the constructs were analyzed by radioligand binding in particulate preparations of transiently transfected HEK293 cells using the agonist [3H]des-Arg10-kallidin and the antagonist (3H]NPC17731. The ability of these constructs to transmit an intracellular signal was measured in transiently transfected A10 cells, a vascular smooth muscle cell line, by single cell Ca2+ imaging. Substitution of B1 TM-VI into the B2 receptor (B2(B1VI)) dramatically reduced the affinity of the B2-selective agonist BK, whereas the affinity of the B2-selective antagonist NPC17731 was unaltered. High affinity BK binding was fully regained when two residues, Tyr259 and Ala263, near the extracellular surface of TM-VI in B2(B1VI), were replaced with the corresponding residues in the wild-type B2 receptor, which are Phe259 and Thr263. The construct B1(B2VI), produced by substitution of B2 TM-VI into the B1 receptor, did not support high affinity binding of the B1-selective agonist des-Arg10-kallidin. In contrast to BK and des-Arg10-kallidin, the binding of the less subtype-selective agonist kallidin showed little sensitivity to TM-VI exchange. These results show that TM-VI in the human B1 and B2 BK receptor subtypes, although only 36% identical, are structurally compatible. Furthermore, this domain contributes significantly to the ability of these receptors to discriminate between the subtype-selective agonists BK and des-Arg10-kallidin.

Ämnesord och genrebeteckningar

Biuppslag (personer, institutioner, konferenser, titlar ...)

  • Mathis, Sandra A. (författare)
  • Leeb-Lundberg, L. M.FredrikUniversity of Texas(Swepub:lu)mphy-fle (författare)
  • University of Texas (creator_code:org_t)

Sammanhörande titlar

  • Ingår i:Journal of Biological Chemistry: ASBMB272:1, s. 311-3170021-9258

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Leeb, Tosso
Mathis, Sandra A ...
Leeb-Lundberg, L ...
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Lunds universitet

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