Neuropeptide Y in mammalian genital tract: localization and biological action

Abstract

Neuropeptide Y, NPY, is one of the most common neuropeptides in mammalian and seems to influence many physiological systems significantly, e.g. the cardiovascular system and the gastrointestinal system. In the present investigation the distribution, localization and physiological effects of NPY were studied in the mammalian genital tract, primarily the female. In the human female genital tract the highest concentrations of NPY-immunoreactivity, NPY-IR, measured by radioimmunoassay, were demonstrated in the uterine artery, the ovary, the Fallopian tube, and the vagina. Immunohistochemical investigations demonstrated the highest density of NPY immunoreactive nerve fibers in relation to blood vessels, although some NPY-IR nerves also were seen close to non-vascular smooth muscle. In the ovary, many NPY-IR nerves were observed in connection with follicles. The NPY-IR material throughout the genital tract was identical to synthetic, amidated human NPY as evaluated by gel filtration, high performance liquid chromatography, and isoelectric focusing. Pro-NPY and NPY-IR material was also demonstrated in human plasma and follicular fluid. NPY induced only a weak direct contractile effect on small cervical arteries from humans investigated in vitro by isometric tension measurements. NPY had no effect on smooth muscle specimens either from the salpinx or the uterus. The 133Xe washout method was evaluated on the rabbit ovary in order to measure changes in the ovary blood flow rate in vivo. A mono-exponential washout curve for 133Xe was found for the whole washout process, ensuring that the blood flow rate at any time could be calculated from the curve. Injection of NPY close to ovarian artery resulted in a dose dependent decrease in the ovarian blood flow rate with a maximum reduction to 40% of the control blood flow rate. In vitro investigation of the rabbit ovarian artery demonstrated only a weak direct contractile effect of NPY but a significant potentiation of the NA response was observed. In vessels precontracted with NA, it was demonstrated that NPY was a potent inhibitor of vasoactive intestinal peptide-induced relaxation. The postsynaptic contractile NPY effects in the rabbit ovarian artery were most likely mediated through a NPY Y1 receptor as demonstrated by the effect of the selective NPY Y1 receptor agonist [Leu31,Pro34]NPY and the Y2 receptor agonist, NPY11-36. The presynaptic inhibitory effect of NPY on the vas deferens motor response induced by electrical stimulation was possibly caused by stimulation of NPY Y2 receptors as evaluated by the effect of the above mentioned peptide analogs in this system.(ABSTRACT TRUNCATED AT 400 WORDS)