This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Pinto, F. M. Articles by Luz Candenas, M. Search for Related Content PubMed PubMed Citation Articles by Pinto, F. M. Articles by Luz Candenas, M.

Tachykinin Receptor and Neutral Endopeptidase Gene Expression in the Rat Uterus: Characterization and Regulation in Response to Ovarian Steroid Treatment¹

Centro de Investigaciones Científicas Isla de La Cartuja, Instituto de Investigaciones Químicas, 41092 Sevilla, Spain; and Departamento de Genética, Facultad de Biología, Universidad de La Laguna, 38206 Tenerife, Spain

Address all correspondence and requests for reprints to: Dr. Francisco M. Pinto, Instituto de Investigaciones Científicas Isla de La Cartuja, Instituto de Investigaciones Químicas, Avenida Americo Vespuccio s/n, 41092 Sevilla, Spain. E-mail: mluz{at}cica.es

Tachykinin neuropeptides, such as substance P, are localized to a population of sensory fibers that innervate the mammalian female reproductive tract. In the present study, we have characterized tachykinin NK₁ receptor (NK₁R), NK₂ receptor (NK₂R), and NK₃ receptor (NK₃R) gene expression by semiquantitative RT-PCR in uteri from ovariectomized rats and studied their regulation in response to 17ß-estradiol (E₂), progesterone (P₄), or a combination of both. In addition, we analyzed the expression and regulation of the neutral endopeptidase 24.11 (NEP), the most important enzyme involved in tachykinin degradation in the rat uterus. In uteri from control (olive oil-treated) rats, RT-PCR assays revealed single bands corresponding to the expected product sizes encoding complementary DNA for NK₁R (232 bp), NK₂R (491 bp), NK₃R (325 bp), and NEP (221 bp). The identity of the amplified fragments was confirmed by DNA sequence analysis. Compared with control rats, NK₁R messenger RNA (mRNA) was increased by 2-fold in uteri from rats treated with E₂, was decreased by 3.3-fold in rats treated with P₄, and was decreased by 1.8-fold in rats treated with both E₂ and P₄. Uterine NK₂R mRNA levels were not altered by any steroid treatment. E₂ treatment decreased by 15-fold NK₃R mRNA. P₄ was without effect if administered alone and did not influence the E₂-induced decrease in NK₃R mRNA. NEP mRNA levels were about 4-fold lower in E₂-treated than in P₄-treated rats. Functional studies were carried out in uteri from E₂- or P₄-treated ovariectomized rats to characterize the contractile response evoked by the selective tachykinin receptor agonists [Sar⁹Met(O₂)¹¹]substance P (NK₁R selective), [Nle¹⁰]NKA-(4–10) (NK₂R selective), and [MePhe⁷]NKB (NK₃R selective) in the presence of the NEP inhibitor phosphoramidon (1 µM). A marked correlation was observed between the magnitude of the contractile response to each agonist and the level of expression determined by RT-PCR for each tachykinin receptor. The present findings show that tachykinin NK₁R, NK₂R, NK₃R, and NEP are expressed in the rat uterus and that ovarian steroids differentially regulate their expression.

This article has been cited by other articles:

				V. M. Pereira, F. M. Reis, R. A. S. Santos, G. D. Cassali, S. H. S. Santos, K. Honorato-Sampaio, and A. M. dos Reis Gonadotropin Stimulation Increases the Expression of Angiotensin-(1--7) and Mas Receptor in the Rat Ovary Reproductive Sciences, December 1, 2009; 16(12): 1165 - 1174. [Abstract] [PDF]

				N. O. Belo, M. R. Sairam, and A. M. dos Reis Impairment of the Natriuretic Peptide System in Follitropin Receptor Knockout Mice and Reversal by Estradiol: Implications for Obesity-Associated Hypertension in Menopause Endocrinology, March 1, 2008; 149(3): 1399 - 1406. [Abstract] [Full Text] [PDF]

				M. Seda, F. M Pinto, S. Wray, C. G Cintado, P. Noheda, H. Buschmann, and L. Candenas Functional and Molecular Characterization of Voltage-Gated Sodium Channels in Uteri from Nonpregnant Rats Biol Reprod, November 1, 2007; 77(5): 855 - 863. [Abstract] [Full Text] [PDF]

				R. H. Straub The Complex Role of Estrogens in Inflammation Endocr. Rev., August 1, 2007; 28(5): 521 - 574. [Abstract] [Full Text] [PDF]

				S. Pal, J. Wu, J. K. Murray, S. H. Gellman, M. A. Wozniak, P. J. Keely, M. E. Boyer, T. M. Gomez, S. M. Hasso, J. F. Fallon, et al. An antiangiogenic neurokinin-B/thromboxane A2 regulatory axis J. Cell Biol., September 25, 2006; 174(7): 1047 - 1058. [Abstract] [Full Text] [PDF]

				N.M. Page, J. Dakour, and D.W. Morrish Gene regulation of neurokinin B and its receptor NK3 in late pregnancy and pre-eclampsia Mol. Hum. Reprod., July 1, 2006; 12(7): 427 - 433. [Abstract] [Full Text] [PDF]

				C. Faisy, F. Pinto, C. Danel, E. Naline, P.-A. Risse, I. Leroy, D. Israel-Biet, J.-Y. Fagon, M.-L. Candenas, and C. Advenier beta2-Adrenoceptor Agonist Modulates Endothelin-1 Receptors in Human Isolated Bronchi Am. J. Respir. Cell Mol. Biol., April 1, 2006; 34(4): 410 - 416. [Abstract] [Full Text] [PDF]

				B. Salthun-Lassalle, S. Traver, E. C. Hirsch, and P. P. Michel Substance P, Neurokinins A and B, and Synthetic Tachykinin Peptides Protect Mesencephalic Dopaminergic Neurons in Culture via an Activity-Dependent Mechanism Mol. Pharmacol., November 1, 2005; 68(5): 1214 - 1224. [Abstract] [Full Text] [PDF]

				E. Patak, F. M. Pinto, M. E. Story, C. O. Pintado, A. Fleming, N. M. Page, J. N. Pennefather, and M. L. Candenas Functional and Molecular Characterization of Tachykinins and Tachykinin Receptors in the Mouse Uterus Biol Reprod, May 1, 2005; 72(5): 1125 - 1133. [Abstract] [Full Text] [PDF]

				D. Marzioni, G. Fiore, A. Giordano, M. Nabissi, P. Florio, F. Verdenelli, F. Petraglia, and M. Castellucci Placental Expression of Substance P and Vasoactive Intestinal Peptide: Evidence for a Local Effect on Hormone Release J. Clin. Endocrinol. Metab., April 1, 2005; 90(4): 2378 - 2383. [Abstract] [Full Text] [PDF]

				C. O. Pintado, F. M. Pinto, J. N. Pennefather, A. Hidalgo, A. Baamonde, T. Sanchez, and M. L. Candenas A Role for Tachykinins in Female Mouse and Rat Reproductive Function Biol Reprod, September 1, 2003; 69(3): 940 - 946. [Abstract] [Full Text] [PDF]

				A. P. R. Costa, C. R. Fagundes-Moura, V. M. Pereira, L. F. Silva, M. A. R. Vieira, R. A. S. Santos, and A. M. Dos Reis Angiotensin-(1-7): A Novel Peptide in the Ovary Endocrinology, May 1, 2003; 144(5): 1942 - 1948. [Abstract] [Full Text] [PDF]

				L. H. Crane, M. J. Williams, A. J. Nimmo, and G. P. Hamlin Estrogen-Dependent Regulation of Neurokinin 3 Receptor-Mediated Uterine Contractility in the Rat Biol Reprod, November 1, 2002; 67(5): 1480 - 1487. [Abstract] [Full Text] [PDF]

				S Bradesi, H Eutamene, J Fioramonti, and L Bueno Acute restraint stress activates functional NK1 receptor in the colon of female rats: involvement of steroids Gut, March 1, 2002; 50(3): 349 - 354. [Abstract] [Full Text] [PDF]

				C. G. Cintado, F. M. Pinto, P. Devillier, A. Merida, and M. L. Candenas Increase in Neurokinin B Expression and in Tachykinin NK3 Receptor-Mediated Response and Expression in the Rat Uterus with Age J. Pharmacol. Exp. Ther., December 1, 2001; 299(3): 934 - 938. [Abstract] [Full Text]

				S. McElvy, S. G. Greenberg, J. L. Mershon, D. S. Yang, C. Magill, and K. E. Clark Mechanism of uterine vascular refractoriness to endothelin-1 in pregnant sheep Am J Physiol Heart Circ Physiol, August 1, 2001; 281(2): H804 - H812. [Abstract] [Full Text] [PDF]

				M. L. Candenas, J. Magraner, C. P. Armesto, E. Anselmi, P. M. Nieto, J. D. Martin, C. Advenier, and F. M. Pinto Changes in the Expression of Tachykinin Receptors in the Rat Uterus During the Course of Pregnancy Biol Reprod, August 1, 2001; 65(2): 538 - 543. [Abstract] [Full Text] [PDF]

				M. Trujillo, L. Candenas, C. G. Cintado, J. Magraner, J. Fernandez, J. D. Martín, and F. M. Pinto Hormonal Regulation of the Contractile Response Induced by Okadaic Acid in the Rat Uterus J. Pharmacol. Exp. Ther., March 1, 2001; 296(3): 841 - 848. [Abstract] [Full Text]

				G. P. Hamlin, M. J. Williams, A. J. Nimmo, and L. H. Crane Hormonal Variation of Rat Uterine Contractile Responsiveness to Selective Neurokinin Receptor Agonists Biol Reprod, June 1, 2000; 62(6): 1661 - 1666. [Abstract] [Full Text]