Hormonal variation of rat uterine contractile responsiveness to selective neurokinin receptor agonists

Regulated uterine contractions are important in many reproductive functions such as sperm transport and embryo positioning during implantation The rol e of classical neurotransmitters including acetylcholine and norepinephrine in regulating myometrial contractility has been well studied; however, the peripheral role of sensory neurotransmitters such as the neurokinins is le ss clear The major neurokinins are substance P, neurokinin A, and neurokini n B, which predominantly activate neurokinin receptors (NK-Rs) 1, 2, and 3, respectively. This study utilized selective receptor agonists to examine t he role of NK-Rs in uterine contractility. Uterine tissues, obtained from t he major stages of the rat estrous cycle, were stimulated with selective NK -R agonists. Addition of each agonist resulted in a significant contractile response. However, the magnitude and nature of the response were dependent upon the stage of the estrous cycle, with responses to all agonists being significantly decreased in tissue from proestrus and estrus. Furthermore, t he nature of NK3-R-mediated contraction was different in tissue from proest rus and estrus compared to metestrus and diestrus. The hormonal dependence of NK-R-mediated contractility was then examined in the ovariectomized estr ogen-supplemented rat model. These studies confirmed that the magnitude and nature of uterine contractility in response to NK-R activation depend upon the hormonal environment.