Androgens block outward potassium currents and decrease spontaneous action potentials in GH3 cells

详细信息    查看全文

• 作者：Lorena Suárez ; Usama Bilal ; Javier Bordallo…
• 关键词：Androgens ; Potassium channels ; Voltage ; and Ca2+ ; activated potassium channel ; GH3 cells ; Adenohypophysis
• 刊名：Naunyn-Schmiedeberg's Archives of Pharmacology
• 出版年：2015
• 出版时间：January 2015
• 年：2015
• 卷：388
• 期：1
• 页码：67-78
• 全文大小：7,195 KB
• 参考文献：1. Akaike N, Harata N (1994) Nystatin perforated patch recording and its applications to analyses of intracellular mechanisms. Jpn J Physiol 44(5):433-73 CrossRef
  2. Balthazart J, Schumacher M, Malacarne G (1984) Relative potencies of testosterone and 5 alpha-dihydrotestosterone on crowing and cloacal gland growth in the Japanese quail (Coturnix coturnix japonica). J Endocrinol 100(1):19-3 CrossRef
  3. Barros F, Delgado LM, Macia C, de la Pena P (1991) Effects of hypothalamic peptides on electrical activity and membrane currents of 'patch perforated' clamped GH3 anterior pituitary cells. FEBS Lett 279(1):33-7 CrossRef
  4. Berkefeld H, Sailer CA, Bildl W, Rohde V, Thumfart JO, Eble S, Klugbauer N, Reisinger E, Bischofberger J, Oliver D, Knaus HG, Schulte U, Fakler B (2006) BKCa-Cav channel complexes mediate rapid and localized Ca²⁺?activated K⁺ signaling. Science 314(5799):615-20 CrossRef
  5. Brunton PJ, Sausbier M, Wietzorrek G, Sausbier U, Knaus HG, Russell JA, Ruth P, Shipston MJ (2007) Hypothalamic-pituitary-adrenal axis hyporesponsiveness to restraint stress in mice deficient for large-conductance calcium- and voltage-activated potassium (BK) channels. Endocrinology 148(11):5496-506 CrossRef
  6. Carani C, Granata AR, Fustini MF, Marrama P (1996) Prolactin and testosterone: their role in male sexual function. Int J Androl 19(1):48-4 CrossRef
  7. Carter JN, Tyson JE, Tolis G, Van Vliet S, Faiman C, Friesen HG (1978) Prolactin-screening tumors and hypogonadism in 22 men. N Engl J Med 299(16):847-52 CrossRef
  8. Chomczynski P, Sacchi N (1987) Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem 162(1):156-59 CrossRef
  9. Cohen J (1988) Statistical power analysis for the behavioral sciences. Lawrence Erlbaum Associates, Hillsdale
  10. Deenadayalu VP, White RE, Stallone JN, Gao X, Garcia AJ (2001) Testosterone relaxes coronary arteries by opening the large-conductance, calcium-activated potassium channel. Am J Physiol Heart Circ Physiol 281(4):H1720–H1727
  11. Deenadayalu V, Puttabyatappa Y, Liu AT, Stallone JN, White RE (2011) Testosterone-induced relaxation of coronary arteries: activation of BKCa channels via the cGMP-dependent protein kinase. Am J Physiol Heart Circ Physiol 302(1):H115–H123 CrossRef
  12. Denef C (1983) 5 alpha-dihydrotestosterone formation and its functional significance in rat anterior pituitary, subpopulations of gonadotrophs and cell cultures. J Steroid Biochem 19(1A):235-39 CrossRef
  13. Fakler B, Adelman JP (2008) Control of K(Ca) channels by calcium nano/microdomains. Neuron 59(6):873-81 CrossRef
  14. Fernandes VS, Barahona MV, Recio P, Martinez-Saenz A, Ribeiro AS, Contreras C, Martinez AC, Bustamante S, Carballido J, Garcia-Sacristan A, Prieto D, Hernandez M (2012) Mechanisms involved in testosterone-induced relaxation to the pig urinary bladder neck. Steroids 77(5):394-02 CrossRef
  15. Finkelstein JS, O’Dea LS, Whitcomb RW, Crowley WF Jr (1991a) Sex steroid control of gonadotropin secretion in the human male. II. Effects of estradiol administration in normal and gonadotropin-releasing hormone-deficient men. J Clin Endocrinol Metab 73(3):621-28 CrossRef
  16. Finkelstein JS, Whitcomb RW, O’Dea LS, Longcope C, Schoenfeld DA
• 作者单位：Lorena Suárez (2)
  Usama Bilal (1)
  Javier Bordallo (1) (2)
  Bego?a Cantabrana (1) (2)
  Manuel Sánchez (1) (2) (3)
  
  2. Instituto Universitario de Oncología del Principado de Asturias, Asturias, Spain
  1. Farmacología, Departamento de Medicina, Universidad de Oviedo, Oviedo, Spain
  3. Farmacología, Facultad de Medicina, Julián Clavería 6, Oviedo, 33006, Spain
  
• 刊物类别：Biomedical and Life Sciences
• 刊物主题：Biomedicine
  Pharmacology and Toxicology
  Neurosciences
  
• 出版者：Springer Berlin / Heidelberg
• ISSN：1432-1912

文摘

Androgens produce nongenomic effects in several cells by different mechanisms, including ion channel modulation. Adenohypophyseal cells express several K+ channels, including voltage and Ca2+-dependent K+ (BK) channels, which might be the target of androgens to modulate cellular action potentials and hormonal secretion. Androgen effects were studied in GH3 cells (from anterior pituitary rat tumor) by means of the patch-clamp technique. Cells were continuously perfused with saline solution, in the absence or presence of the androgens studied, while applying 40?mV pulses of 400?ms from a holding potential of ?0?mV in whole-cell configuration with nystatin-perforated patches. Androgens reversibly blocked noninactivating K+ currents in a concentration-dependent manner without a latency period and with an order of efficacy of: 5β-dihydrotestosterone (DHT)>testosterone>5α-DHT. RT-PCR showed two isoforms of the α-pore forming subunits of BK channels. These channels are responsible for one third of the noninactivating current, according to the blockade of paxilline, a selective BK antagonist. Androgens seem to directly interact with BK channels since they were blocked in excised inside-out patches and independent of the whole-cell configuration and the NO-cGMP-dependent pathway. Testosterone, but not 5α- or 5β-DHT, increased BK currents in HEK-293 cells overexpressing the short isoform, suggesting a cellular selectivity based on the α-subunits. The effect on noninactivating currents may be responsible for the decrease of spontaneous action potential frequency. Long-term cellular incubation with testosterone did not modify noninactivating currents density in GH3 cells. It is remarkable that 5β-DHT, a reductase metabolite with weak androgenic activity, was the most efficient blocker.