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Functional and Molecular Characterization of Tachykinins and Tachykinin Receptors in the Mouse Uterus¹

Department of Anaesthesia,⁴ Royal Women's Hospital, Carlton, Victoria 3053, Australia Centro de Investigaciones Científicas Isla de La Cartuja,⁵ Instituto de Investigaciones Químicas, Sevilla 41092, Spain Department of Pharmacology,⁶ Monash University, Clayton, Victoria 3800, Australia School of Animal and Microbial Sciences,⁷ University of Reading, Reading RG6 6AJ, United Kingdom Department of Pharmaceutical Biology and Pharmacology,⁸ Victorian College of Pharmacy, Monash University, Parkville, Victoria 3052, Australia

The aim of this study was to analyze the function and expression of tachykinins, tachykinin receptors, and neprilysin (NEP) in the mouse uterus. A previous study showed that the uterotonic effects of substance P (SP), neurokinin A (NKA), and neurokinin B (NKB) in estrogen-treated mice were mainly mediated by the tachykinin NK₁ receptor. In the present work, further contractility studies were undertaken to determine the nature of the receptors mediating responses to tachykinins in uteri of late pregnant mice. Endpoint and real-time quantitative RT-PCR were used to analyze the expression of the genes that encode the tachykinins SP/NKA, NKB, and hemokinin-1 (HK-1) (Tac1, Tac2, and Tac4); and the genes that encode tachykinin NK₁ (Tacr1), NK₂ (Tacr2), and NK₃ (Tacr3) receptors in uteri from pregnant and nonpregnant mice. The data show that the mRNAs of tachykinins (particularly NKB and HK-1), tachykinin receptors, and NEP are locally expressed in the mouse uterus, and their expression changes during the estrous cycle and during pregnancy. The tachykinin NK₁ receptor is the predominant tachykinin receptor in the nonpregnant and early pregnant mouse and may mediate tachykinin-induced uterine contractions in the nonpregnant mouse. The tachykinin NK₂ receptor is predominant in the late pregnant mouse and is the main receptor mediating uterotonic responses to tachykinins at late pregnancy. The tachykinin NK₃ receptor is expressed in considerable amounts only in uteri from nonpregnant diestrous animals, and its physiological significance remains to be clarified.

female reproductive tract, mouse, neuroendocrinology, pregnancy, signal transduction, tachykinin NK₂ receptor, tachykinins, uterus

² Correspondence: M. Luz Candenas, Centro de Investigaciones Científicas Isla de La Cartuja, Instituto de Investigaciones Químicas, Avda. Americo Vespucio s/n, 41092 Sevilla, Spain. FAX: 34 95 446 0565; luzcandenas{at}iiq.csic.es

³ Correspondence: Jocelyn N Pennefather, Department of Pharmaceutical Biology and Pharmacology, Victorian College of Pharmacy, Monash University, Parkville, Victoria 3052, Australia. FAX: 61 39 833 3754; jocelyn.oneil{at}vcp.monash.edu.au