Compound | Structure | Cloned human receptors | Cloned rabbit receptors | Cloned mouse receptors | ||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
−4 | −3 | −2 | −1 | 0 | 1 | 2 | 3 | 4 | 5 | 6 | 7 | 8 | 9 | B1R2-a | B2R2-b | B1R2-c | B2R2-d | B1R2-e | B2R2-f | |
Native kinins (B2R agonists) | ||||||||||||||||||||
BK | Arg | Pro | Pro | Gly | Phe | Ser | Pro | Phe | Arg | 2000 | 0.54 | >5000 | 4.5 | 2002-g | 0.48 | |||||
Lys-BK | Lys | Arg | Pro | Pro | Gly | Phe | Ser | Pro | Phe | Arg | 42 | 0.63 | 19 | 2 | 510 | 0.52 | ||||
Met-Lys-BK | Met | Lys | Arg | Pro | Pro | Gly | Phe | Ser | Pro | Phe | Arg | 70 | 2.1 | 16 | 3.6 | |||||
B1R agonists | ||||||||||||||||||||
des-Arg9-BK | Arg | Pro | Pro | Gly | Phe | Ser | Pro | Phe | 720 | 8100 | 32 | >1000 | 0.7 | 8.1 | ||||||
Lys-des-Arg9-BK | Lys | Arg | Pro | Pro | Gly | Phe | Ser | Pro | Phe | 0.2 | >30000 | 0.23 | >1000 | 1.7 | 6400 | |||||
Sar-[d-Phe8]des-Arg9-BK | Sar2-h | Arg | Pro | Pro | Gly | Phe | Ser | Pro | d-Phe | 682-i | ||||||||||
Tyr-Gly-Lys-Aca-Lys-des-Arg9-BK | Tyr | Gly | Lys | Aca | Lys | Arg | Pro | Pro | Gly | Phe | Ser | Pro | Phe | 0.22-j | ||||||
Peptide B2R antagonist | ||||||||||||||||||||
Hoe 140 | d-Arg | Arg | Pro | Hyp | Gly | Thi | Ser | d-Tic | Oic | Arg | >10000 | 0.41 | >5000 | 2 | >10000 | 0.23 | ||||
NPC 17731 | d-Arg | Arg | Pro | Hyp | Gly | Phe | Ser | X2-k | Oic | Arg | 1262-l | 0.182-m | ||||||||
B1R antagonists | ||||||||||||||||||||
[Leu8]des-Arg9-BK | Arg | Pro | Pro | Gly | Phe | Ser | Pro | Leu | 440 | >30000 | 80 | 4.1 | >30000 | |||||||
Lys-[Leu8]des-Arg9-BK | Lys | Arg | Pro | Pro | Gly | Phe | Ser | Pro | Leu | 1.3 | >30000 | 0.43 | >100 | 7.5 | >30000 | |||||
Ac-Lys-[MeAla6, Leu8]des-Arg9-BK | Ac-Lys | Arg | Pro | Pro | Gly | Phe | Me-Ala | Pro | Leu | 6702-n | >100002-n | >50002-n | >100002-n | |||||||
R-715 | Ac-Lys | Arg | Pro | Pro | Gly | Phe | Ser | βD-Nal | Ile | 0.662-n | >100002-n | 412-n | >100002-n | |||||||
Mixed B1 and B2R antagonists | ||||||||||||||||||||
Hoe 140-des-Arg | d-Arg | Arg | Pro | Hyp | Gly | Thi | Ser | d-Tic | Oic | 60 | 27 | 24 | ||||||||
NPC 18565 | d-Arg | Arg | Pro | Hyp | Gly | Phe | Ser | X2-k | Oic | 0.072-l | 26.12-o | |||||||||
B9858 | Lys | Lys | Arg | Pro | Hyp | Gly | Igl | Ser | d-Igl | Oic | 0.042-n | 1462-n | 5.42-n | 442-n | ||||||
B9430 | d-Arg | Arg | Pro | Hyp | Gly | Igl | Ser | d-Igl | Oic | Arg | 12.62-p | 0.252-p | 2482-n | 0.332-n | ||||||
Nonpeptide B2R antagonists | ||||||||||||||||||||
WIN 64338 | [[4-[[2-[[bis(cyclohexylamino)methylene]amino]-3-(2-naphthyl)-1-oxopropyl]amino]phenyl]methyl]tributylphosphonium chloride monohydrochloride | 642-q | 150 | |||||||||||||||||
FR 173657 | 8-[3-[N-[(E)-3-(6-acetamidopyridin-3-yl)acryloylglycyl]-N-methylamino]-2,6-dichlorobenzyloxy]-2-methylquinoline | >100002-r | 8.92-r |
↵2-a Nanomolar affinity estimates are IC50 values from binding competition with 1 nM [3H]Lys-des-Arg9-BK to transiently expressed human B1R in COS-7 cells. From Menke et al. (1994), except if otherwise indicated. Other comparative estimates based on cloned human B1Rs are found elsewhere (Bastian et al., 1997; Aramori et al., 1997; Austin et al., 1997).
↵2-b Nanomolar affinity estimates are IC50 values from binding competition with 100 pM [3H]BK to stably expressed human B2R in CHO cells. From Hess et al. (1994), except if otherwise indicated. Other comparative estimates are found elsewhere (Aramori et al., 1997).
↵2-c Nanomolar affinity estimates are IC50 values from binding competition with 0.5 nM [3H]Lys-[Leu8]des-Arg9-BK to transiently expressed rabbit B1R in COS-7 cells. From MacNeil et al. (1995), except if otherwise indicated.
↵2-d Nanomolar affinity estimates are IC50 values from binding competition with 1 nM [3H]BK to transiently expressed rabbit B2R in COS-1 cells (Bachvarov et al., 1995).
↵2-e Nanomolar affinity estimates are Ki values from binding competition with [3H]Lys-des-Arg9-BK to transiently expressed murine B1R in COS cells. From Hesset al. (1996), except if otherwise indicated. Other comparative estimates are found elsewhere (Pesquero et al., 1996).
↵2-f Nanomolar affinity estimates are IC50 values from binding competition with 100 pM [3H]BK to transiently expressed murine B2R in COS cells (Hess et al., 1994).
↵2-g Pesquero et al. (1996) also report an IC50 of about 200 nM, but the value is much higher (>1 μM) if the assay is run in the presence of the kininase I inhibitor mergepta, suggesting that the formation of des-Arg9-BK may distort the estimate.
↵2-h Abbreviations: Ac, N-acetyl; Aca, ε-aminocaproic acid; Hyp, 4-hydroxy-l-proline; Igl, α-(2-indanyl)glycine; β-Nal: β-2-naphthylalanine; Oic, octahydroindole-2-carboxylic acid; Thi, β-2-thienylalanine; Tic, 1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid; Sar, sarcosine (N-methyl-glycine).
↵2-i Nanomolar IC50 value from the binding competition of 1 nM [125I]Tyr-Gly-Lys-Aca-Lys-des-Arg9-BK to wild type rabbit B1R in cultured aortic SMCs (Levesque et al., 1995a).
↵2-j KD value for the iodinated form of the peptide in a saturation binding assay to wild type rabbit B1R in cultured aortic SMCs; (Levesque et al., 1995a).
↵2-k X = D-HypEtrans-propyl.
↵2-l Nanomolar Ki value from the binding competition of 1 nM [3H]Lys-des-Arg9-BK to transiently expressed human B1R in HEK 293 cells (Leeb et al., 1997).
↵2-m Nanomolar KD value for binding of [3H]NPC 17731 to transiently expressed human B2R in HEK 293 cells (Leebet al., 1997).
↵2-n Data from MacNeil et al. (1997). Kivalues derived from human B2R stably transfected in CHO cells, or human or murine B1R or murine B2R transiently transfected in COS cells.
↵2-o Nanomolar Ki value from the binding competition of 1 nM [3H]NPC 17731 to transiently expressed human B2R in HEK 293 cells (Leeb et al., 1997).
↵2-p Nanomolar IC50 value from the binding competition of 0.5 nM [3H]Lys-des-Arg9-BK to wild type human B1R in IMR-90 cells or of 0.3 nM [3H]BK to stably expressed human B2R in CHO cells. (Gera et al., 1996; Stewart et al., 1996).
↵2-q Ki value from binding competition with 1–2 nM [3H]BK to wild type human B2R in IMR-90 cells (Sawutzet al., 1994).
↵2-r Nanomolar affinity estimates are IC50 values from binding competition with 500 pM of either [3H]Lys-des-Arg9-BK (B1R) or [3H]BK (B2R) to stably expressed human receptors in CHO cells (Aramoriet al., 1997).