Measurement of calcium mobilization in CHO cells
195–227; (b) A. Toba, T. Yokomizo and T. Shimizu, Prostaglandins
& Other Lipid Mediators, 2002, 68–69, 575–585; (c) T. Yokomizo, K.
Masuda, K. Toda, T. Izumi and T. Shimizu, Am. J. Respir. Crit. Care
Med., 2000, 161, S51–55; (d) T. Yokomizo, T. Izumi and T. Shimizu,
Arch. Biochem. Biophys., 2001, 385, 231–241; (e) T. Yokomizo, K.
Kato, K. Terawaki, T. Izumi and T. Shimizu, J. Exp. Med., 2000, 192,
421–431.
5 R. J. Aiello, P. A. Bourassa, S. Lindsey, W. Weng, A. Freeman and
H. J. Showell, Arterioscler., Thromb., Vasc. Biol., 2002, 22, 443–449;
A. Mennander, S. Tiisala, J. Ustinov, A. Ra¨isa¨nen, T. Paavonen and
P. Ha¨yry, Arterioscler. Thromb., 1992, 12, 1380–1386.
6 H. Takatsuka, Y. Takemoto, S. Yamada, T. Wakae, A. Mori, M.
Okada, N. Iwata and T. Okamoto, Drugs Exp. Clin. Res., 2002, 28,
121–125; M. Tanaka, T. Tamaki, Y. Konoeda, Y. Uchida, T. Kaizu
and A. Kawamura, Transplant. Proc., 2000, 32, 2340.
7 L. Iversen, K. Kragballe and V. A. Ziboh, Skin Pharmacol., 1997,
10, 169–177.
8 W.-G. Tong, X.-Z. Ding, R. Hennig, R. C. Witt, J. Standop, P. M.
Pour and T. E. Adrian, Clin. Cancer Res., 2002, 8, 3232–3242; M.-H.
Yoo, H. Song, C.-H. Woo, H. Kim and J.-H. Kim, Oncogene, 2004,
23, 9259–9268.
9 Y. Kurihara, H. Endo, T. Akahoshi and H. Kondo, Clin. Exp.
Immunol., 2001, 123, 323–330; A. Hashimoto, H. Endo, I. Hayashi,
Y. Murakami, H. Kitasato, S. Kono, T. Matsui, S. Tanaka, A.
Nishimura, K. Urabe, M. Itoman and H. Kondo, J. Rheumatol.,
2003, 30, 1712–1718; Y. Murakami, T. Akahoshi, I. Hayashi, H.
Endo, A. Hashimoto, S. Kono, H. Kondo, S. Kawai, M. Inoue and
H. Kitasato, Arthritis Rheum., 2003, 48, 2931–2941; R. Alten, E.
Gromnica-Ihle, C. Pohl, J. Emmerich, J. Steffgen, R. Roscher, R.
Sigmund, B. Schmolke and G Steinmann, Ann. Rheum. Dis., 2004,
63, 170–176.
CHO cells stably expressing human BLT131 or BLT22f, seeded on
a 96-well glass-bottom plate (Coster 3603) at 4 × 104 cells per
well, were loaded with 4 lM Fluo-3 (Dojin, Kumamoto, Japan)
in 1 × HBSS (Hanks balanced salt solution, Sigma) containing
◦
0.04% pluoronic acid and 1% FCS at 37 C for 1 h. The cells
were washed twice with 1 × HBSS and pretreated with various
concentrations of antagonists diluted in 100 ll of 1 × HBSS,
1% FCS for 30 min. A stock of BLT antagonists was prepared
in DMSO solution, and the final concentration of DMSO in
the assay was adjusted to 0.1% in all wells. To each well was
added 50 ll (or 150 ll) of 300 nM LTB4 (Cayman Chem.) to
give a final concentration of 100 nM (or 300 nM), and the LTB4-
dependent increase in fluorescent intensity was measured using
FlexStation (Molecular Devices). CHO cells transfected with an
empty vector did not respond to 100 nM LTB4 (data not shown).
Acknowledgements
This work was supported in part by a grant from the Ministry
of Education, Culture, Sports, Science and Technology for the
“University–Industry Joint Research” Project (2004–2008). We
thank the staff of the instrumental analysis center of Mukogawa
1
Women’s University for the H-NMR and MS measurements
and elemental analyses.
References
10 Several heteroaromatic and cyclized aliphatic compounds as an LTB4
antagonist were reported previously: (a) D. Delorme, Y. Ducharme,
C. Brideau, C.-C. Chan, N. Chauret, S. Desmarais, D. Dube, J.-P.
Falgueyret and R. Relean, J. Med. Chem., 1996, 39, 3951–3970. (L
708780, naphthalene derivative with furan ring); (b) S. W. Djuric,
S. H. Docter, S. S. Yu, D. Spangler, B. S. Tsai, C. P. Anglin, T. S.
Gaginella, J. F. Kachur and R. H. Keith, Bioorg. Med. Chem. Lett.,
1994, 4, 811–816. (SC-53228, benzopyran derivative); (c) S. W. Djuric,
P. W. Collins, P. T. Jones, R. L. Shone, B. S. Tsai, D. J. Fretland, G. M.
Butchko, D. Villani-Prince and R. H. Keith, J. Med. Chem., 1989,
32, 1145–1147. (SC 41939, benzopyran derivative); (d) T. S. Shoupe,
S. M. Coutts, D. C. Baker and E. S. Hand, Can. Pat. Appl., 1991,
63 pp. CPXXEB CA 2013960, AA 19910319, CAN 115:158949, AN
1991: 558949. (PF 10042, dibenzofuran derivative); (e) C. D. Wright,
P. J. Kuipers, M. D. Hoffman, D. O. Thueson and M. C. Conroy,
Biochem. Biophys. Res. Commun., 1990, 167, 828–834. (CI 949, indole
derivative); (f) J. M. Musser, U. R. Chakraborty, S. Sciortino, R. J.
Gordon, A. Khandwala, E. S. Neiss, T. P. Pruss, R. V. Inwegen, I.
Weinryb and S. M. Coutts, J. Med. Chem., 1997, 30, 96–104. (PF
5901, quinoline derivative); (g) C. Can, M. G. Cinar, S. Ulker, A.
Evinc and S. Kosay, Eur. J. Pharmacol., 1998, 350, 223–228. (MK
886, indole derivative); (h) J. M. Poudrel, P. Hullot, J. P. Vidal, J. P.
Girard, J. C. Rossi, A. Muller and C. Bonne, Bioorg. Med. Chem.
Lett., 1996, 6, 2349–2354.
1 Part of this work has been published as a preliminary communication:
K. Ando, E. Tsuji, Y. Ando, J. Kunitomo, M. Yamashita, S. Ohta,
T. Nabe, S. Kohno, T. Yokomizo, T. Shimizu and Y. Ohishi, Org.
Biomol. Chem., 2004, 2, 3427–3431.
2 (a) C. R. Turner, R. Breslow, M. J. Conklyn, C. J. Andresen, D. K.
Patterson and A. Lopez-Anaya, J. Clin. Invest., 1996, 97, 381–387;
(b) P. Sharon and W. F. Stenson, Gastroenterology, 1984, 86, 453–
460; (c) A. Nakao, K. Nasaka, N. Ohishi, E. Noiri, T. Suzuki and S.
Taniguchi, Kidney Int., Suppl., 1997, 63, S236–238; (d) R. J. Griffiths,
E. R. Pettipher, K. Kock, C. A. Farrell, R. Breslow and M. Conklyn,
Proc. Natl. Acad. Sci. USA, 1995, 92, 517–521; (e) R. P. Gladue, L. A.
Carroll, A. J. Milici, D. N. Scampoli, H. A. Stukenbrok and E. R.
Pettipher, J. Exp. Med., 1996, 183, 1893–1898; (f) T. Yokomizo, K.
Kato, K. Terawaki, T. Izumi and T. Shimizu, J. Exp. Med., 2000, 192,
421–431.
3 CP-195543: (a) L. A. Reiter, K. Koch, A. D. Piscopio, H. J. Showell,
R. Alpert, M. S. Biggers, R. J. Chambers, M. J. Conklyn, K. Cooper,
S. R. Cortina, J. N. Dibrino, B. W. Dominy, C. A. Farrell, G. P.
Hingorani, G. J. Martinelli, M. Ramchandani and K. F. Wright,
Bioorg. Med. Chem. Lett., 1998, 8, 1781–1786. CP-105696:; (b) K.
Koch, L. S. Melvin, Jr., L. A. Reiter, M. S. Biggers, H. J. Showell, R. J.
Griffiths, E. R. Pettipher, J. B. Cheng, A. J. Milici and R. Breslow,
J. Med. Chem., 1994, 37, 3197–3199. LY-223982:; (c) D. M. Gapinski,
B. E. Mallett, L. L. Froelich and W. T. Jackson, J. Med. Chem.,
1999, 33, 2807–2813; (d) W. T. Jackson, R. J. Boyd, L. L. Froelich,
D. M. Gapinski, B. E. Mallett and J. S. Sawyer, J. Med. Chem.,
1993, 36, 1726–1734. LY-255283:; (e) D. K. Herron, T. Goodson,
N. G. Bollinger, D. Swanson-Bean, I. G. Wright, G. S. Staten, A. R.
Thompson, L. L. Froelich and W. T. Jackson, J. Med. Chem., 1992,
35, 1818–1828; (f) J. S. Sawyer, N. J. Bach, S. R. Baker, R. F. Baldwin,
P. S. Borromeo, S. L. Cockerham, J. H. Fleisch, P. Floreancig, L. L.
Froelich and W. T. Jackson, J. Med. Chem., 1995, 38, 4411–4432.
ONO-4057:; (g) K. Kishikawa, S. Nakao, S. Matsumoto, K. Kondo
and N. Hamanaka, Adv. Prostaglandin, Thromboxane, Leukotriene
Res., 1995, 23, 279–281; (h) K. Kishikawa, N. Tateishi, T. Maruyama,
R. Seo, M. Toda and T. Miyamoto, Prostaglandins, 1992, 44, 261–
275. ZK-158252:; (i) R. D. Pallavi, K. H. Abdelmadjid, P. Mai, D. S.
Wolf-Dieter, M. S. Bruce and W. Walter, J. Biol. Chem., 1999, 274,
23341–23348; (j) M. Matousek, K. Mitsube, M. Mikuni and M.
Brannstrom, Mol. Hum. Reprod., 2001, 7, 35–42. 1,3-Disubstituted
cyclohexane:; (k) J.-M. Poudrel, P. Hullot, J.-P. Vidal, J.-P. Girard, J.-
C. Rossi, A. Muller, C. Bonne, V. Bezuglov, I. Serkov, P. Renard and B.
Pfeiffer, J. Med. Chem., 1999, 42, 5289–5310. BIIL315:; (l) F. W. Birke,
C. J. Meade, R. Anderskewitz, G. A. Speck and H.-M. Jennewein,
J. Pharmacol. Exp. Ther., 2002, 297, 458–466. LY293111:; (m) M.
Philip, S. J. Scott, F. L. Larry, M. L. Larry and S. M. Stephen,
Biochem. Pharmacol., 1995, 49, 1683–1690.
11 H. Nakai, M. Konno, S. Kosuge, S. Sakuyama, M. Toda, Y. Arai,
T. Obata, N. Katsube, T. Miyamoto, T. Okegawa and A. Kawasaki,
J. Med. Chem., 1988, 31, 84–91.
12 (a) E. Tsuji, K. Ando, J. Kunitomo, M. Yamashita, S. Ohta, S. Kohno
and Y. Ohishi, Org. Biomol. Chem., 2003, 1, 3139–3141; (b) K. Ando,
E. Tsuji, Y. Ando, N. Kuwata, J. Kunitomo, M. Yamashita, S. Ohta,
S. Kohno and Y. Ohishi, Org. Biomol. Chem., 2004, 2, 625–635.
13 P. D. Greenspan, A. J. Main, S. S. Bhagwat, L. I. Barsky, R. A.
Doti, A. R. Eagle, L. M. Frey, H. Zhou, K. E. Lipson, M. H. Chin,
R. H. Jackson and S. Uziel-Fusi, Bioorg. Med. Chem. Lett., 1997,
7, 949–954; P. D. Greenspan, R. A. Fujimoto, P. J. Marshall, A.
Raychaudhuri, K. E. Lipson, H. Zhou, R. A. Doti, D. V. Coppa, L.
Zhu, R. Pelletier, S. Uziel-Fusi, R. H. Jackson, M. H. Chin, B. L.
Kotyuk and J. J. Fitt, J. Med. Chem., 1999, 42, 164–172.
14 Y. Ohishi, T. Mukai, M. Nagahara, M. Yajima and N. Kajikawa,
Chem. Pharm. Bull., 1989, 37, 2393–2405.
15 The 3-H signal (7.73 ppm) showed no NOE correlation between other
aromatic signals (6.9 ppm, d and 7.4 ppm, d) of 1b. This supported
the structure of 1b.
16 M. Watanabe, S. Hisamatsu, H. Hotokezaka and S. Furukawa, Chem.
Pharm. Bull., 1986, 34, 2810–2820.
17 (a) J. Boutagy and R. Thomas, Chem. Rev., 1974, 74, 87–99;
(b) N. Matsuura, Y. Yashiki, S. Nakashima, M. Maeda and S.
Sasaki, Heterocycles, 1999, 51, 975–978; (c) J. K. F. Geirsson, B.
¨
4 (a) C. Brink, S.-E. Dahlen, J. F. Evans, D. W. P. Hay, S. Nicosia, C. N.
Serhan, T. Shimizu and T. Yokomizo, Pharmacol. Rev., 2003, 55,
O. Gudmundsson and R. Sigurdardottir, Acta Chem. Scand., 1993,
47, 1112–1116.
2 1 3 8
O r g . B i o m o l . C h e m . , 2 0 0 5 , 3 , 2 1 2 9 – 2 1 3 9