Investigation of the specificity of FK 888 as a tachykinin NK1 receptor antagonist.
1. A recently described peptide tachykinin (NK1) 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 pIC50 value was 6.6 +/- 0.08. 2. Contractions induced by a selective NK1 receptor agonist, [Sar9,Met(O2)11]substance P, were inhibited competitively by FK 888; the pKB value was 7.1. 3. FK 888 (1 nM-100 microM) 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 nM-30 microM) or noradrenaline (0.1-100 microM), were not affected by 10 microM FK 888. 4. FK 888 (1-30 microM) did not induce histamine release from rat peritoneal mast cells. 5. FK 888 (33 and 333 microM) 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 (NK1) receptor antagonist.
Wang
Z Y
ZY
Department of Pharmacology, University of Lund, Sweden.
Tung
S R
SR
Strichartz
G R
GR
Håkanson
R
R
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D004151:Dipeptides / Q000494:pharmacology*; D005260:Female; D006168:Guinea Pigs; D006636:Histamine Release / Q000187:drug effects; D066298:In Vitro Techniques; D007211:Indoles / Q000494:pharmacology*; D007498:Iris / Q000187:drug effects / Q000502:physiology; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D064729:Neurokinin-1 Receptor Antagonists; D011817:Rabbits; D011892:Rana catesbeiana; D012584:Sciatic Nerve / Q000187:drug effects / Q000502:physiology
D004151:Dipeptides; D007211:Indoles; D064729:Neurokinin-1 Receptor Antagonists; C078949:FK 888