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Localization of Bradykinin B₂ Receptors in the Endometrium and Myometrium of Rat Uterus and the Effects of Estrogen and Progesterone¹

Howard Florey Institute of Experimental Physiology and Medicine, University of Melbourne (C.M., S.Y.C., F.A.O.M.), Parkville, Victoria 3052, Australia; Institute of Physiological Chemistry and Pathobiochemistry, Johannes-Gutenberg University (W.M.-E.), Mainz D-55099, Germany; and the Center for Molecular Biotechnology, School of Life Sciences, Queensland University of Technology (J.C.), Brisbane, Queensland 4001, Australia

Address all correspondence and requests for reprints to: Dr. C. Murone, Department of Anatomical Pathology, Austin and Repatriation Medical Center, Level 6, Harold Stokes Building, Austin Campus, Heidelberg, Victoria 3084, Australia. E-mail: carmel.murone{at}ludwig.edu.au

In the uterus, bradykinin is a potent inducer of smooth muscle contraction, which is mediated by the bradykinin B₂ receptor subtype. However, little is known about the distribution or regulation of this receptor in this tissue. The aim of this study was to localize the B₂ receptor in the uterus and determine whether the levels of this receptor were altered during the estrous cycle and modulated by estrogen and/or progesterone in ovariectomized rats.

At diestrus, uterine B₂ receptors were localized to both the circular and longitudinal smooth muscle layers of the myometrium, the endometrial stroma, the glandular epithelium, and the layer subjacent to the luminal epithelium. B₂ receptor levels in both myometrium and endometrium were lowest during early proestrus, when estrogen levels are low, whereas myometrial B₂ receptor protein and messenger RNA levels were highest during late proestrous, when estrogen levels peak. Similar findings were observed for the estrogen-supplemented group after ovariectomy, with progesterone appearing to inhibit the estrogen-induced rise in bradykinin B₂ receptor density in estrogen/progesterone-treated animals.

Using in vitro receptor autoradiography employing the specific B₂ receptor antagonist analog, HPP-HOE140, immunostaining with specific antipeptide antibodies generated against the B₂ receptor, and in situ hybridization using a specific bradykinin B₂ receptor riboprobe, our findings show a discrete distribution of the bradykinin B₂ receptor throughout the different layers of the uterus and suggest that bradykinin B₂ receptor levels in the rat uterus are regulated by estrogen, and possibly progesterone, in both myometrium and endometrium.

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