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BOR - Papers in Press, published online ahead of print January 12, 2005.
Biol Reprod 2005, 10.1095/biolreprod.104.036814
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Submitted October 4, 2004
Returned for revision October 24, 2004
Accepted December 20, 2004

Female Reproductive Tract


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

Eva Patak , Francisco M. Pinto , Margot E. Story , C. Oscar Pintado , Anna Fleming , Nigel M. Page , Jocelyn N. Pennefather , and M. Luz Candenas *

* To whom correspondence should be addressed. E-mail: luzcandenas{at}iiq.csic.es.

Abstract
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. End-point 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 non-pregnant 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 non-pregnant and early pregnant mouse and may mediate tachykinin-induced uterine contractions in the non-pregnant 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 non-pregnant diestrous animals and its physiological significance remains to be clarified.

Key words: Female Reproductive Tract • Neuroendocrinology • Pregnancy • Signal transduction • Uterus


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