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We have discovered a novel cyclopeptide substance P (SP) antagonist, FK 224 (N-[N2-[N-[N-[N-[2,3-didehydro-N-methyl-N-[N-[3-(2-pentylphenyl )- propionyl]-L-threonyl]tyrosyl-L-leucynyl]-D-phenylalanyl]-L-allo- threonyl]-L-asparaginyl]-L-serine-nu-lactone), which inhibited [3H]SP binding to guinea pig lung membranes in a dose-dependent manner. According to Rosenthal analysis, the inhibitory effect of FK 224 on [3H]SP binding appears to be competitive. In order to clarify the receptor subtype selectivity of FK 224, we have studied the interaction of FK 224 with three tachykinin receptors (NK1, NK2 and NK3) by using receptor binding techniques and in vitro bioassays, and have also compared FK 224 with the novel nonpeptide antagonist, (+/-)-CP-96,345. In binding experiments, FK 224 dose-dependently inhibited [3H]SP binding to rat cerebral cortical membranes (NK1) and [3H]neurokinin (NK) A (NKA) binding to rat duodenum smooth muscle membranes (NK2), but did not affect [3H]eledoisin binding to rat cerebral cortical membranes (NK3). In bioassay experiments, FK 224 inhibited SP-induced contraction of guinea pig ileum (NK1) and NKA-induced contraction of rat vas deferens (NK2) in a dose-dependent manner, but did not affect NKB-induced contraction of rat portal vein (NK3). In contrast, (+/-)-CP-96,345 inhibited SP-induced contraction of guinea pig ileum, but not NKA-induced contraction of rat vas deferens or NKB-induced contraction of rat portal vein. In the presence of FK 224, SP dose-response curves and NKA dose-response curves were shifted to the right in parallel with no depression of the maximal contraction.(ABSTRACT TRUNCATED AT 250 WORDS)
H Morimoto, and
M Murai, and
Y Maeda, and
M Yamaoka, and
M Nishikawa, and
S Kiyotoh, and
T Fujii
June 1996,
Immunopharmacology,
H Morimoto, and
M Murai, and
Y Maeda, and
M Yamaoka, and
M Nishikawa, and
S Kiyotoh, and
T Fujii
September 1995,
The American journal of physiology,
H Morimoto, and
M Murai, and
Y Maeda, and
M Yamaoka, and
M Nishikawa, and
S Kiyotoh, and
T Fujii
May 1995,
European journal of pharmacology,
H Morimoto, and
M Murai, and
Y Maeda, and
M Yamaoka, and
M Nishikawa, and
S Kiyotoh, and
T Fujii
January 1991,
Science (New York, N.Y.),
H Morimoto, and
M Murai, and
Y Maeda, and
M Yamaoka, and
M Nishikawa, and
S Kiyotoh, and
T Fujii
November 1993,
Anesthesiology,
H Morimoto, and
M Murai, and
Y Maeda, and
M Yamaoka, and
M Nishikawa, and
S Kiyotoh, and
T Fujii
February 2004,
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology,
H Morimoto, and
M Murai, and
Y Maeda, and
M Yamaoka, and
M Nishikawa, and
S Kiyotoh, and
T Fujii
December 2003,
Expert opinion on pharmacotherapy,
H Morimoto, and
M Murai, and
Y Maeda, and
M Yamaoka, and
M Nishikawa, and
S Kiyotoh, and
T Fujii
December 1995,
European journal of pharmacology,
H Morimoto, and
M Murai, and
Y Maeda, and
M Yamaoka, and
M Nishikawa, and
S Kiyotoh, and
T Fujii
March 2003,
Neuropharmacology,
H Morimoto, and
M Murai, and
Y Maeda, and
M Yamaoka, and
M Nishikawa, and
S Kiyotoh, and
T Fujii
November 2006,
European journal of pharmacology,
