Dactinomycin analogues as neurokinin-2 receptor antagonists.
Dactinomycin has recently been shown to be a competitive neurokinin-2 receptor antagonist in addition to its inhibiting action on DNA replication. We investigated in the isolated guinea-pig bronchi the action of 3 Dactinomycin analogues on the contractions evoked by the selective neurokinin-2 receptor agonist [Nle10] neurokinin A(4-10). These analogues included 4,4'-Gly-Dactinomycin and the single peptide lactone of dactinomycin which are inactive on DNA replication and 5,5'-MeLeu-Dactinomycin, which has potent antitumour activity. Independently of their known effect on DNA replication, the three analogues showed neurokinin-2 antagonistic activity which was lower than for Dactinomycin.
Auberson
S
S
Department of Physiology and Pharmacology, Karolinska Institute, Stockholm, Sweden.
Mauger
A B
AB
Lundberg
J M
JM
D000818:Animals; D001980:Bronchi / Q000187:drug effects; D004261:DNA Replication / Q000187:drug effects; D003609:Dactinomycin / Q000031:analogs & derivatives / Q000494:pharmacology*; D005260:Female; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D018041:Receptors, Neurokinin-2 / Q000037:antagonists & inhibitors*
D018041:Receptors, Neurokinin-2; D003609:Dactinomycin