Actinomycin D is a competitive and selective antagonist at NK2 tachykinin receptors.
The ability of actinomycin D, a known antineoplastic agent, to affect NK1 NK2 and NK3 tachykinin (TK) receptor types was assessed on several in vitro bioassays. Actinomycin D was completely ineffective as a TK antagonist in the guinea-pig ileum longitudinal muscle (GPI) and on the rat portal vein (RPV) (two issues containing NK1, and NK3 TK receptors, respectively) while it was a weak competitive antagonist in the endothelium-denuded rabbit pulmonary artery (RPA) and in the hamster trachea (HT) (tissues containing the NK2A and NK2B receptor subtypes, respectively). Furthermore actinomycin D was able to displace [125I]-His-NKA from NK2 receptor sites of the rat small intestine smooth muscle membranes. Although actinomycin D is about 3 orders of magnitude weaker as an NK2 antagonist as compared to the most effective ligands available, it could represent a starting point in the development of non-peptidic NK2 receptor antagonists.
Patacchini
R
R
Pharmacology Department, A. Menarini Pharmaceuticals, Florence, Italy.
Astolfi
M
M
Brown
M C
MC
Maggi
C A
CA
D000818:Animals; D001667:Binding, Competitive; D006224:Cricetinae; D003609:Dactinomycin / Q000378:metabolism / Q000494:pharmacology*; D006168:Guinea Pigs; D007082:Ileum / Q000187:drug effects / Q000502:physiology; D008297:Male; D008647:Mesocricetus; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology; D015288:Neurokinin A / Q000378:metabolism; D011169:Portal Vein / Q000187:drug effects / Q000502:physiology; D011651:Pulmonary Artery / Q000187:drug effects / Q000502:physiology; D011817:Rabbits; D051381:Rats; D011919:Rats, Inbred Strains; D017981:Receptors, Neurotransmitter / Q000037:antagonists & inhibitors*; D018039:Receptors, Tachykinin; D014132:Trachea / Q000187:drug effects / Q000502:physiology
D017981:Receptors, Neurotransmitter; D018039:Receptors, Tachykinin; D003609:Dactinomycin; D015288:Neurokinin A