Dactinomycin is a competitive neurokinin-2 receptor antagonist.
Dactinomycin, a peptide antibiotic from Streptomyces spp., is a classical agent which inhibits DNA replication. In the present study, dactinomycin inhibited specific [125I]NKA binding in rat colon membranes (KI = 1.05 x 10(-5) M) in a competitive manner. Furthermore, dactinomycin caused a parallel rightward shift of the concentration-response curve for the contractions in the rat colon induced by the NK-2 receptor agonist [Nle10]-NKA(4-10). A selective inhibition of NK-2 receptors by dactinomycin was supported by the absence of inhibition of NK-1 receptors activation in guinea pig vas deferens and of NK-3 receptors in rat portal vein. The structural similarity of the cyclic peptide moieties of dactinomycin to L-659,877, a known NK-2 receptor antagonist, can probably account for the present observations.
Delay-Goyet
P
P
Department of Pharmacology, Karolinska Institute, Stockholm, Sweden.
Lundberg
J M
JM
D000595:Amino Acid Sequence; D000818:Animals; D002462:Cell Membrane / Q000378:metabolism; D003106:Colon / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D003609:Dactinomycin / Q000494:pharmacology*; D005260:Female; D006168:Guinea Pigs; D066298:In Vitro Techniques; D007700:Kinetics; D008297:Male; D008969:Molecular Sequence Data; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology*; D015288:Neurokinin A / Q000378:metabolism* / Q000494:pharmacology; D011169:Portal Vein / Q000187:drug effects / Q000502:physiology; D051381:Rats; D011919:Rats, Inbred Strains; D018041:Receptors, Neurokinin-2; D017981:Receptors, Neurotransmitter / Q000037:antagonists & inhibitors / Q000187:drug effects / Q000502:physiology*; D015320:Tachykinins / Q000494:pharmacology; D014649:Vas Deferens / Q000187:drug effects / Q000502:physiology
D018041:Receptors, Neurokinin-2; D017981:Receptors, Neurotransmitter; D015320:Tachykinins; D003609:Dactinomycin; D015288:Neurokinin A