ArticleBritish journal of pharmacology2002
Pharmacological and functional characterization of the guinea-pig B2 bradykinin receptor stably expressed in CHO-K1 cell line.
Article in British journal of pharmacology, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
In the present study, pharmacological properties of a bradykinin B(2) receptor amplified either from guinea-pig ileum or lung and homologous to the previously reported sequence except two amino-acid changes L(124)-->P and N(227)-->Y in the receptor protein were characterized. Tritiated bradykinin ([(3)H]-BK) specifically bound to the cloned guinea-pig B(2) bradykinin receptor stably expressed in Chinese hamster ovary cells (CHO-K1) with a K(D) value of 0.29+/-0.07 nM. In competition experiments, bradykinin (BK) affinity constant value was 0.21+/-0.05 nM while the two specific kinin B(1) ligands, des-Arg(9)-bradykinin (DBK) and des-Arg(9)-Leu(8)-bradykinin (DLBK) were unable to compete with [(3)H]-BK. As the specific peptide antagonist D-Arg-[Hyp(3),Thi(5),D-Tic(7),Oic(8)]-bradykinin (HOE140), (E)-3-(6-acetamido-3-pyridil)-N-[-N-[2,4-dichloro-3-[(2-methyl-8-quinolinyl)oxymethyl]phenyl]-N-methylaminocarbonylmethyl]acrylamide (FR173657) and 1-[[3-[2,4-dimethylquinolin-8-yl)oxymethyl] - 2,4 - dichloro - phenyl]sulfonyl] - 2(S) - [[4-[4-(aminoiminomethyl)-phenylcarbonyl]piperazin-1-yl]carbonyl]pyrrolidine (LF16-0335C) exhibited a high affinity for this receptor with K(i) values of 7.34+/-2.45 nM and 8.54+/-1.55 nM respectively. BK and kallidin (KD) increased inositol phosphates (IPs) levels with EC(50) values of 0.44+/-0.12 nM and 6.88+/-0.28 nM, respectively. Neither DLBK nor DBK (0.01 nM to 10 microM) stimulated or inhibited IPs turnover and as expected HOE140 did not raise IPs production. HOE140 (0.1 microM) and LF 16-0335c (1 microM) right shifted the BK response curve with pK(B) values of 9.2+/-0.4 and 8.4+/-0.3, respectively. The results indicate that this cloned guinea-pig receptor displayed typical pharmacological properties of a bradykinin B(2) receptor and support the existence of a single B(2) receptor in this species.
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