ABSTRACT
The receptors for neurokinin 1 (NK1-R), neurokinin 2 (NK2-R), and neurokinin 3 (NK3-R) are expressed and functionally active in the uterus, promoting strong contractions of the myometrium. Previously, we demonstrated that myometrial contractility activated by the NK-Rs is regulated by estrogen. In the current study, we furthered our investigations of the role of estrogen in the regulation of NK3-R-mediated myometrial contractility. Estrogen promotes both heterologous and homologous desensitization of NK3-R-mediated uterine contractility. In tissue obtained from estrogen-dominated rats (ovariectomized estrogen-treated rats and rats in estrus), the magnitude of uterine contractions decreased in response to consecutive additions of the NK3-R-selective agonist senktide. By addition of the fourth dose of agonist, the contractile response was routinely barely above baseline. In contrast, in tissue obtained from non-estrogen-dominated rats consecutive doses of senktide resulted in contractions of identical magnitude. The homologous desensitization was specific to the NK3-R, and the desensitization of the NK3-R-mediated response did not affect the magnitude or nature of uterine contractions in response to NK1-R or NK2-R activation. Furthermore, heterologous and homologous desensitization of NK3-R-mediated contractility is dependent upon the duration of exposure to estrogen. This complex mechanism appears to be important in intact tissue; capsaicin-mediated release of endogenous neuropeptides resulted in a desensitization of response to subsequent stimulation with senktide in estrogen-dominated uterine tissue.
Subject(s)
Estrogens/physiology , Receptors, Neurokinin-3/metabolism , Substance P/analogs & derivatives , Uterine Contraction/physiology , Acetylcholine/pharmacology , Animals , Capsaicin/pharmacology , Dose-Response Relationship, Drug , Estrogens/pharmacology , Estrus/physiology , Female , In Vitro Techniques , Ovariectomy , Peptide Fragments/pharmacology , Rats , Rats, Sprague-Dawley , Receptors, Neurokinin-1/drug effects , Receptors, Neurokinin-1/metabolism , Receptors, Neurokinin-2/drug effects , Receptors, Neurokinin-2/metabolism , Receptors, Neurokinin-3/agonists , Substance P/pharmacology , Uterine Contraction/drug effects , Uterus/drug effects , Uterus/physiologyABSTRACT
Videolaparoscopy was used to visualize the reproductive tract contractility of the squirrel monkey, Saimiri sciureus. This technique gives information on the nature, direction of propagation, duration, and frequency of contractions. At the times of ovulation, and embryo entry to the uterus, contractile activity was observed in both the uterus and oviduct, with the latter being more frequent. The dominant direction of propagation was towards the utero-tubal junction, and simultaneous contractions were frequently observed in both uterus and oviduct. © 1992 Wiley-Liss, Inc.
