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Journal of Molecular Neuroscience

, Volume 40, Issue 1–2, pp 127–134 | Cite as

Muscarinic Acetylcholine Receptor Subtypes in the Male Reproductive Tract

Expression and Function in Rat Efferent Ductules and Epididymis
  • Maria Christina W. Avellar
  • Erica R. Siu
  • Fabiana Yasuhara
  • Elisabeth Maróstica
  • Catarina S. Porto
Article

Abstract

In mammals, at least five different muscarinic acetylcholine receptor subtypes (mAChRs; M1–M5) are known to be widely expressed and distributed in different tissues from different species. They mediate distinct physiological functions according to their location and receptor subtype. Multiple events are associated with the regulation of intracellular signaling by mAChRs, and a coordinated balance of the molecular mechanisms governing receptor signaling, desensitization, resensitization, and mitogenic signaling is known to occur in various cell types. Most of the actions of acetylcholine (ACh) in the male reproductive tract are induced by its effects on mAChRs, but the role of specific mAChR subtypes on male reproductive function and fertility are still not well understood. The rat efferent ductules and epididymis are androgen-dependent tissues of the male reproductive tract, with important roles in the process to form a viable and fertile sperm. In the present study, aspects of the expression, localization, and potential function of mAChR subtypes in rat efferent ductules and epididymis are reviewed. Furthermore, evidences for the implication of mAChRs in the regulation of protein synthesis and secretion in these tissues are presented. Taken together, the studies contribute to our understanding about physiological aspects of mAChR and mechanisms by which the cholinergic system affects male reproduction.

Keywords

Muscarinic acetylcholine receptor Epididymis Efferent ductules Male reproductive tract Acetylcholine 

Notes

Acknowledgements

This work was supported by grants from Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP). C.S.P. and M.C.W.A. were research fellows from Conselho Nacional de Desenvolvimento Cientifico e Tecnológico (CNPq). Fellowships were supported by Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES; E.R.S. and F.Y.) and FAPESP (E. M.). We thank E.M.J.S. Santos and M. Silva for technical assistance.

References

  1. Ban, Y., Sato, T., Nakatsuka, T., Kemi, M., Samura, K., Matsumoto, H., et al. (2002). Impairment of male fertility induced by muscarinic receptor antagonists in rats. Reproductive Toxicology, 16, 757–765.CrossRefPubMedGoogle Scholar
  2. Baumgarten, H. G., Falck, B., Holstein, A. F., Owman, C., & Owman, T. (1968). Adrenergic innervation of the human testis, epididymis, ductus deferens and prostate: a fluorescence microscopic and fluorometric study. Z. Zellforsch, 90, 81–95.CrossRefPubMedGoogle Scholar
  3. Bishop, M. R., Sastry, B. V., Schmidt, D. E., & Harbison, R. D. (1976). Occurrence of choline acetyltransferase and acetylcholine and other quaternary ammonium compounds in mammalian spermatozoa. Biochemical Pharmacology, 25, 1617–1622.CrossRefPubMedGoogle Scholar
  4. Bonner, T. I., Buckley, N. J., Young, A. C., & Brann, M. R. (1987). Identification of a family of muscarinic acetylcholine receptor genes. Science, 237, 527–532.CrossRefPubMedGoogle Scholar
  5. Borges, M. O., Abreu, M. L., Porto, C. S., & Avellar, M. C. W. (2001). Characterization of muscarinic acetylcholine receptor in rat Sertoli cells. Endocrinology, 142, 4701–4710.CrossRefPubMedGoogle Scholar
  6. Brooks, D. E. (1981). Secretion of proteins and glycoprotiens by the rat epididymis: regional differences, anfrogen-dependence and effects of proteins inhibitors, procaine and tunicamycin. Biology of Reproduction, 25, 1099–1117.CrossRefPubMedGoogle Scholar
  7. Bruschini, H., Schmidt, R. A., & Tanagho, E. A. (1978). Neurologic control of prostatic secretion in the dog. Investigative Urology, 15, 288–290.PubMedGoogle Scholar
  8. Caulfield, M. P., & Birdsall, N. J. M. (1998). International Union of Pharmacology. XVII. Classification of muscarinic acetylcholine receptors. Pharmacological Reviews, 50, 279–290.PubMedGoogle Scholar
  9. Cooper, T. G. (1995). Role of the epididymis in mediating changes in the male gamete during maturation. Advances in Experimental Medicine and Biology, 377, 87–101.PubMedGoogle Scholar
  10. Cooper, T. G. (1998). Interactions between epididymal secretions and spermatozoa. Journal of Reproduction and Fertility. Supplement, 53, 119–136.PubMedGoogle Scholar
  11. Dacheux, J. L., Castella, S., Gatti, J. L., & Dacheux, F. (2005). Epididymal cell secretory activities and the role of proteins in boar sperm maturation. Theriogenology, 63, 319–341.CrossRefPubMedGoogle Scholar
  12. Du, J. Y., Zuo, W. L., Chen, M. H., Xiang, H., & Zhou, W. L. (2006). Involvement of muscarinic acetylcholine receptors in chloride secretion by cultured rat epididymal epithelium. Cell Biology International, 30, 741–746.CrossRefPubMedGoogle Scholar
  13. Dwivedi, C., & Long, N. J. (1989). Effect of cholinergic agents on human spermatozoa motility.Biochem. Med. Metab. Biol., 42, 66–70.CrossRefGoogle Scholar
  14. Eglen, R. M. (2006). Muscarinic receptor subtype in neuronal and non-neuronal cholinergic function. Auton. Autacoid Pharmacol., 6, 219–233.CrossRefGoogle Scholar
  15. El-Badawi, A., & Schenk, E. A. (1967). The distribution of cholinergic and adrenergic nerves in the mammalian epididymis. A comparative histochemical study. American Journal of Anatomy, 121, 1–14.CrossRefPubMedGoogle Scholar
  16. Ehrén, I., Sjöstrand, N. O., Hammarström, M., & Wiklund, N. P. (1997). Is glandular formation of nitric oxide a prerequisite for muscarinic secretion of fructose in the guinea-pig seminal vesicle? Urological Research, 25, 433–438.CrossRefPubMedGoogle Scholar
  17. Florman, H. M., & Storey, B. T. (1982). Mouse gamete interactions: the zona pellucida is the site of the acrosome reaction leading to fertilization in vitro. Developmental Biology, 91, 121–130.CrossRefPubMedGoogle Scholar
  18. Gatti, J. L., Castella, S., Daucheux, F., Ecroyd, H., Métayer, S., Thimon, V., et al. (2004). Posttesticular sperm enviroment and fertility. Animal Reproduction Science, 82–83, 321–339.CrossRefPubMedGoogle Scholar
  19. Gerendai, I., Tóth, I. E., Kocsis, K., Boldogkoi, Z., Rusvai, M., & Haláz, B. (2001). Identification of CNS neurons involved in the innervation of the epididymis: a viral transneuronal tracing study. Auton. Neurosci., 92, 1120–1126.Google Scholar
  20. Goodman, D., & Harbison, R. (1981). Characterization of enzymatic acetylcholine synthesis by mouse brain, rat sperm, and purified carnitine acetyltransferase. Biochemical Pharmacology, 30, 1521–1528.CrossRefPubMedGoogle Scholar
  21. Goodman, D., Adatsi, F., & Harbison, R. (1984). Evidence for the extreme overestimation of choline acetyltransferase in human sperm, human seminal plasma and rat heart: a case of mistaking carnitine acetyltransferase for choline acetyltransferase. Chemico-Biological Interactions, 49, 39–53.CrossRefPubMedGoogle Scholar
  22. Grando, S. A. (1997). Biological functions of keratinocyte cholinergic receptors. Journal of Investigative Dermatology Symposium Proceedings, 2, 41–48.Google Scholar
  23. Hamamura, M., Maróstica, E., Avellar, M. C. W., & Porto, C. S. (2006). Muscarinic acetylcholine receptor subtypes in the rat seminal vesicle. Molecular and Cellular Endocrinology, 247, 192–198.CrossRefPubMedGoogle Scholar
  24. Hansen, L. A., Dacheux, F., Man, S. Y., Clulow, J., & Jones, R. C. (2004). Fluid reabsorption by the ductuli efferentes testis of the rat is dependent on both sodium and chlorine. Biology of Reproduction, 71, 410–416.CrossRefPubMedGoogle Scholar
  25. Hodson, N. (1965). Sympathetic nerves and reproductive organs in the male rabbit. Journal of Reproduction and Fertility, 10, 209–220.PubMedGoogle Scholar
  26. Hodson, N. (1970). The nerves of the testis, epididymis and scrotum. In A. D. Johnson, W. R. Gomes & N. L. Vandemark (Eds.), The Testis, Vol I (pp. 47–99). New York: Academic.Google Scholar
  27. Hinton, B. T., Lan, Z. J., Lye, R. J., & Labus, J. C. (2000). Regulation of epididymal function by testicular factors: the lumicrine hypothesis. In E. Goldberg (Ed.), The Testis: From Stem Cell to Sperm Function (pp. 63–173). Massachusetts, NJ: Norwell.Google Scholar
  28. Hulme, E. C., Birdsall, N. J. M., & Buckley, N. J. (1990). Muscarinic receptor subtypes. Annual Review of Pharmacology and Toxicology, 30, 633–673.CrossRefPubMedGoogle Scholar
  29. Ibanez, C. F., Pelto-Huikko, M., Soder, O., Ritzen, E. M., Hersh, L. B., Hokfelt, T., et al. (1991). Expression of choline acetyltransferase mRNA in spermatogenic cells results in an accumulation of the enzyme in the postacrosomal region of mature spermatozoa. Proceedings of the National Academy of Sciences of the United States of America, 88, 3676–3680.CrossRefPubMedGoogle Scholar
  30. Ilio, K. Y., & Hess, R. A. (1994). Structure and function of the ductuli efferentes: a review. Microscopy Research and Technique, 29, 432–467.CrossRefPubMedGoogle Scholar
  31. Jimenez-Trejo, F., Tapia-Rodriguez, M., Queiróz, D. B. C., Padilla, P., Avellar, M. C. W., Manzano, P. R., et al. (2007). Serotonin concentration, synthesis, cell origin, and targets in the rat caput epididymis during sexual maturation and variations associated with adult mating status: morphological and biochemical studies. Journal of Andrology, 28, 136–149.CrossRefPubMedGoogle Scholar
  32. Karczmar, A. G. (1963). Ontogenesis of cholinesterases. In G. B. Koelle (Ed.), Cholinesterases and Anticholinesterase Agents. Hanbck. of Exper. Pharmacol., Erganzangswk., vol. 15 (pp. 129–186). Berlin: Springer.Google Scholar
  33. Kumazawa, T., Mizumura, K., & Sato, J. (1987). Response properties of polymodal receptors studied using in vitro testis superior spermatic nerve preparations of dogs. Journal of Neurophysiology, 57, 702–711.PubMedGoogle Scholar
  34. Kinghorn, E. M., Bate, A. S., & Higgins, S. J. (1987). Growth of rat seminal vesicle epithelial cells in culture: neurotransmitters are required for androgen-regulated synthesis of tissue-specific secretory proteins. Endocrinology, 121, 1678–1688.CrossRefPubMedGoogle Scholar
  35. Laitinen, L., & Talo, A. (1981). Effects of adrenergic and cholinergic drugs on electrical and mechanical activities of the rat cauda epididymis in vitro. Journal of Reproduction and Fertility, 63, 205–209.PubMedGoogle Scholar
  36. Lau, W. A. K., & Pennefather, J. N. (1998). Muscarinic receptor subtypes in the rat prostate gland. European Journal of Pharmacology, 343, 151–156.CrossRefPubMedGoogle Scholar
  37. Lau, W. A. K., Pennefather, J. N., & Mitchelson, F. J. (2000). Cholinergic facilitation of neurotransmission to the smooth muscle of the guinea-pig prostate gland. British Journal of Pharmacology, 130, 1013–1020.CrossRefPubMedGoogle Scholar
  38. Lockwood, D. H., & Williams-Ashman, H. G. (1971). Cholinergic-stimulated alkaline phosphatase secretion and phospholipid synthesis in guinea pig seminal vesicles. Journal of Cellular Physiology, 77, 7–15.CrossRefPubMedGoogle Scholar
  39. Longhurst, P. A., & Brotcke, T. P. (1989). Effects of castration and diabetes mellitus on cholinergic responsiveness and muscarinic receptors in the rat vas deferens. Journal of Urology, 141, 1225–1229.PubMedGoogle Scholar
  40. Lucas, T. F., Avellar, M. C. W., & Porto, C. S. (2004). Effects of carbachol on rat Sertoli cell proliferation and muscarinic acetylcholine receptors regulation: an in vitro study. Life Sciences, 75, 1761–1773.CrossRefPubMedGoogle Scholar
  41. Lucas, T. F. G., Siu, E. R., Royer, C., Trindade, C. S., Nader, H. B., Lazari, M. F. M., et al. (2008). Muscarinic acetylcholine receptors: relevance to infertility and male contraception. Immun. Endoc. & Metab. Agents in Med. Chem., 8, 42–50.Google Scholar
  42. Luthin, G. R., Wang, P., Zhou, H., Dhanasekaran, D., & Ruggieri, M. R. (1997). Role of m1 receptor G-protein coupling in cell proliferation in the prostate. Life Sciences, 60, 963–968.CrossRefPubMedGoogle Scholar
  43. Maróstica, E., Guaze, E. F., Avellar, M. C. W., & Porto, C. S. (2001). Characterization of muscarinic acetylcholine receptors in rat epididymis. Biology of Reproduction, 65, 1120–1126.CrossRefPubMedGoogle Scholar
  44. Maróstica, E., Avellar, M. C. W., & Porto, C. S. (2005). Effects of testosterone on muscarinic acetylcholine receptors in the rat epididymis. Life Sciences, 77, 656–669.CrossRefPubMedGoogle Scholar
  45. Meizel, S., & Son, J. H. (2005). Studies of sperm from mutant mice suggesting that two neurotransmitter receptors are important to the zona pellucida-initiated acrosome reaction. Molecular Reproduction and Development, 72, 250–258.CrossRefPubMedGoogle Scholar
  46. Miranda, H. F., Duran, E., Bustamante, D., Paeile, C., & Pinardi, G. (1994). Pre- and postjunctional muscarinic receptor subtypes in the vas deferens of rat. General Pharmacology, 25, 1643–1647.PubMedGoogle Scholar
  47. Miranda, H. F., Duran, E., Fernandez, E., & Pinardi, G. (1995). Muscarinic receptor subtypes in the bisected vas deferens of the rat. General Pharmacology, 26, 387–391.CrossRefPubMedGoogle Scholar
  48. Nadelhaft, I. (2003). Cholinergic axons in the rat prostate and neurons in the pelvic ganglion. Brain Research, 989, 52–57.CrossRefPubMedGoogle Scholar
  49. Nathanson, N. M. (2008). Synthesis, trafficking and localization of muscarinic acetylcholine receptors. Pharmacology and Therapeutics, 119, 33–43.CrossRefPubMedGoogle Scholar
  50. Nouhouayi, Y., & Negulesco, I. (1985). Adrenergic innervation of the smooth muscle cells of the cauda epididymis of the mouse. Acta Anatomica, 121, 59–62.PubMedGoogle Scholar
  51. Orgebin-Crist, M. C., Jahad, N., & Hoffman, L. H. (1976). The effects of testosterone, 5-alpha- dihydrotestosterone, 3alpha-androstanediol, and 3beta-androstanediol on the maturation of rabbit epididymal spermatozoa in organ culture. Cell and Tissue Research, 167, 515–525.CrossRefPubMedGoogle Scholar
  52. Pennefather, J. N., Lau, W. A., Mitchelson, F., & Ventura, S. (2000). The autonomic and sensory innervation of the smooth muscle of the prostate gland: a review of pharmacological and histological studies. Journal of Autonomic Pharmacology, 20, 193–206.CrossRefPubMedGoogle Scholar
  53. Pholpramool, C., & Triphrom, N. (1984). Effects of cholinergic and adrenergic drugs on intraluminal pressures and contractility of the rat testis and epididymis in vivo. Journal of Reproduction and Fertility, 71, 181–188.PubMedCrossRefGoogle Scholar
  54. Picarelli, Z. P., Hyppolito, N., & Valle, J. R. (1962). Synergistic effect of 5-hydroxytriptamine on response of rat seminal vesicle to adrenaline and noradrenaline. Archives Internationales de Pharmacodynamie, 138, 354–363.Google Scholar
  55. Proskocil, B. J., Sekhon, H. S., Jia, Y., Savchenko, V., Blakely, R. D., Lindstrom, J., et al. (2004). Acetylcholine is an autocrine or paracrine hormone synthesized and secreted by airway bronchial epithelial cells. Endocrinology, 145, 2498–506.CrossRefPubMedGoogle Scholar
  56. Ricker, D. D. (1998). The autonomic innervation of the epididymis: its effects on epididymal function and fertility. Journal of Andrology, 19, 1–4.PubMedGoogle Scholar
  57. Robaire, B., & Hermo, L. (1988). Efferent Ducts, Epididymis, and Vas Deferens: Structure Functions, and their Regulation. In E. Knobil & J. D. Neill (Eds.), The Physiology of Reproduction, vol. 1 (pp. 999–1080). New York, NY: Raven.Google Scholar
  58. Sato, T., Ban, Y., Uchida, M., Gondo, E., Yamamoto, M., Sekiguchi, Y., et al. (2005). Atropine-induced inhibition of sperm and semen transport impairs fertility in male rats. Journal of Toxicological Sciences, 30, 207–212.CrossRefPubMedGoogle Scholar
  59. Setchell, B. P., Maddocks, S., & Brooks, D. E. (1994). Anatomy, Vasculature, Innervation, and Fluids of the Male Reproductive Tract. In E. Knobil & J. Neill (Eds.), The Physiology of Reproduction (2nd ed., pp. 1063–1175). New York: Raven.Google Scholar
  60. Shapiro, E., Miller, A. R., & Lepor, H. (1985). Down-regulation of the muscarinic cholinergic receptor of the rat prostate following castration. Journal of Urology, 134, 179–182.PubMedGoogle Scholar
  61. Silva, A. M., Queiróz, D. B. C., Castro Neto, E. F., Naffah-Mazzacoratti, M. G., Godinho, R. O., Porto, C. S., et al. (2002). Segment-specific decrease of both catecholamine concentration and acetylcholinesterase activity are accompanied by nerve refinement in the rat cauda epididymis during sexual maturation. Journal of Andrology, 23, 374–383.PubMedGoogle Scholar
  62. Siu, E. R., Yasuhara, F., Maróstica, E., Avellar, M. C. W., & Porto, C. S. (2006). Expression and localization of muscarinic acetylcholine receptor subtypes in the rat efferent ductules and epididymis. Cell and Tissue Research, 323, 157–166.CrossRefPubMedGoogle Scholar
  63. Stewart, T. A., & Forrester, I. T. (1978). Acetylcholinesterase and choline acetyltransferase in ram spermatozoa. Biology of Reproduction, 19, 271–279.CrossRefPubMedGoogle Scholar
  64. Ventura, S., & Pennefather, J. N. (1991). Sympathetic co-transmission to the cauda epididymis of the rat: characterization of postjunctional adrenoceptors and purinoceptors. British Journal of Pharmacology, 102, 540–544.PubMedGoogle Scholar
  65. Ventura, S., Pennefather, J., & Mitchelson, F. (2002). Cholinergic innervation and function in the prostate gland. Pharmacology and Therapeutics, 94, 93–112.CrossRefPubMedGoogle Scholar
  66. Vreeburg, J. T., Holland, M. K., & Orgebin-Crist, M. C. (1992). Binding of epididymal proteins to rat spermatozoa in vivo. Biology of Reproduction, 47, 588–597.CrossRefPubMedGoogle Scholar
  67. Wang, J. M., McKenna, K. E., McVary, K. T., & Lee, C. (1991). Requirement of innervation for maintenance of structural and functional integrity in the rat prostate. Biology of Reproduction, 44, 1171–1176.CrossRefPubMedGoogle Scholar
  68. Wang, J. M., McKenna, K. E., & Lee, C. (1991). Determination of prostatic secretion in rats: effect of neurotransmitters and testosterone. Prostate, 18, 289–301.CrossRefPubMedGoogle Scholar
  69. Wess, J. (2004). Muscarinic acetylcholine receptor knockout mice: novel phenotypes and clinical implications. Annual Review of Pharmacology and Toxicology, 44, 423–450.CrossRefPubMedGoogle Scholar
  70. Wess, J., Eglen, R. M., & Gautam, D. (2007). Muscarinic acetylcholine receptors: mutant mice provide new insights for drug development. Nature Reviews, 6, 721–728.CrossRefPubMedGoogle Scholar
  71. Wessler, I., & Kirkpatric, C. J. (2008). Acetylcholine beyond neurons: the non-neuronal cholinergic system in humans. British Journal of Pharmacology, 154, 1558–1571.CrossRefPubMedGoogle Scholar
  72. Wessler, I., Kirkpatrick, C. J., & Racke, K. (1998). Non-neuronal acetylcholine, a locally acting molecule, widely distributed in biological systems: expression and function in humans. Pharmacology and Therapeutics, 77, 59–79.CrossRefPubMedGoogle Scholar
  73. Young, R. J., & Laing, J. C. (1991). The binding characteristics of cholinergic sites in rabbit spermatozoa. Molecular Reproduction and Development, 28, 55–61.CrossRefPubMedGoogle Scholar

Copyright information

© Humana Press 2009

Authors and Affiliations

  • Maria Christina W. Avellar
    • 1
  • Erica R. Siu
    • 1
  • Fabiana Yasuhara
    • 1
  • Elisabeth Maróstica
    • 2
  • Catarina S. Porto
    • 1
  1. 1.Section of Experimental Endocrinology, Department of PharmacologyUniversidade Federal de São Paulo-Escola Paulista de MedicinaSão PauloBrazil
  2. 2.Centro de Ciências Médicas, Instìtuto BiomédicoUniversidade Federal FluminenseNiteroiBrasil

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