AbstractThe in vitro contractile effect of neuropeptide Y (NPY) on rat myometrial strips was for the first time demonstrated and characterised, and the EC50value estimated to be 267±87 nM. This effect is presumably mediated by the NPY1receptor being responsible for postsynaptic effects throughout the peripherial nervous system, thus indicating a direct uterotonic effect of NPY. Further, the effect was demonstrated to be dependent on extracellular Ca2+. Short-term exposures to NPY markedly desensitized the tissue affecting subsequent responses to NPY as well as to oxytocin (OT). This desensitization was time-and concentration-dependent, but lasted less than three hours. However, long-term infusions of NPY for 5 days increased the response to both NPY and OT. Long-term infusions of OT caused a marked decrease of the NPY response, and it is concluded that common pathways for up and down regulation of the myometrial responsiveness to several peptide hormones may exist.