Mammalian tachykinins stimulate rat uterus by activating NK-2 receptors.

Neurokinin A (NKA), substance P (SP), and neurokinin B (NKB) enhanced the contractile force of uterine preparations from estrogen-treated rats. Neurokinin A was more and NKB less potent than SP. The actions of SP were enhanced by phosphoramidon (1 microM) but were unaffected by captopril (10 microM) or bestatin (10 microM). The actions of the peptides were enhanced in the combined presence of phosphoramidon, captopril, and bestatin; the potency order remained NKA > SP > NKB. Atropine inhibited responses to NKB but not to NKA, and slightly reduced those to SP. Specific binding of [125I]-iodohistidyl-neurokinin A (INKA) to uterine membranes was displaced by the tachykinins with a potency order of NKA > SP > NKB. These findings indicate that in the rat uterus 1) tachykinins act at an NK-2 receptor, and that another tachykinin receptor on cholinergic nerves may also be present; and 2) endopeptidase-24.11 participates in the inactivation of the tachykinins.