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Investigation of the specificity of FK 888 as a tachykinin NK 1 receptor antagonist
Author(s) -
Wang ZunYi,
Tung Steven R.,
Strichartz Gary R.,
Håkanson Rolf
Publication year - 1994
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1994.tb14892.x
Subject(s) - tachykinin receptor , endocrinology , substance p , medicine , agonist , vas deferens , chemistry , carbachol , nk1 receptor antagonist , receptor antagonist , antagonist , histamine , cholinergic , receptor , biology , neuropeptide
1 A recently described peptide tachykinin (NK 1 ) receptor antagonist, FK 888, was found to inhibit the electrically‐evoked, tachykinin‐mediated contractile responses of the rabbit iris sphincter in a concentration‐dependent manner; the pIC 50 value was 6.6 ±0.08. 2 Contractions induced by a selective NK 1 receptor agonist, [Sar 9 , Met(O 2 ) 11 ]substance P, were inhibited competitively by FK 888; the p K B value was 7.1. 3 FK 888 (1 n m ‐100 μ m ) was without effect on the electrically‐evoked, cholinergic response of the rabbit iris sphincter and the electrically‐evoked, sympathetic response of the guinea‐pig vas deferens. The contractions of the rabbit iris sphincter, induced by either carbachol (10 n m ‐30 μ m ) or noradrenaline (0.1–100 μ m ), were not affected by 10 μ m FK 888. 4 FK 888 (1–30 μ m ) did not induce histamine release from rat peritoneal mast cells. 5 FK 888 (33 and 333 μ m ) was without effect on the electrically‐evoked action potentials of the frog sciatic nerve. Thus, FK 888 is a moderately high affinity and selective tachykinin (NK 1 ) receptor antagonist.