کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
8476318 | 1550805 | 2018 | 49 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Testosterone induces hyporesponsiveness by interfering with IP3 receptors in guinea pig airway smooth muscle
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کلمات کلیدی
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
بیولوژی سلول
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چکیده انگلیسی
Asthma symptoms have been associated with sex steroids. During childhood, this illness seems more frequent in boys than in girls and this tendency reverts in puberty when it is more severe in women. Testosterone (TES), at supraphysiological concentrations, relaxed pre-contracted airway smooth muscle, but its effects at physiological concentrations have not been thoroughly studied. We explored this possibility in guinea pig tracheal smooth muscle. In myocytes TES (10â¯nM) abolished carbachol (CCh)-induced intracellular Ca2+ concentration ([Ca2+]i) increment. Ca2+ responses to ATP were partially modified by TES while histamine's were not. These results indicate that inositol 1,4,5-trisphosphate (IP3) signaling pathway might be involved. Photolysis of caged-IP3 increased [Ca2+]i and TES abolished this effect. TES diminished reactivity of the smooth muscle to CCh and this effect was non-genomic since it was unchanged by flutamide. In tracheal smooth muscle, mRNA for each IP3 receptor (ITPR) isoform was found and, by immunofluorescence, ITPR1 and ITPR3 seems to be the main isoforms observed while ITPR2 was less prominent. Comparing the amino acid sequence of ITPR1 and the sequence of the TES binding site on the androgen receptor, we found that they share a short sequence. This domain could be responsible for the TES binding to the ITPR1 and probably for its blocking effect. We conclude that TES modifies ITPR1 function in airway smooth muscle, turning this tissue less reactive to contractile agonists that act through PLCβ-IP3 signaling cascade. These results might be related to the low asthma prevalence in males from puberty to adulthood.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Molecular and Cellular Endocrinology - Volume 473, 15 September 2018, Pages 17-30
Journal: Molecular and Cellular Endocrinology - Volume 473, 15 September 2018, Pages 17-30
نویسندگان
Luis M. Montaño, Edgar Flores-Soto, Jorge Reyes-GarcÃa, Verónica DÃaz-Hernández, Abril Carbajal-GarcÃa, ElÃas Campuzano-González, G. Lizbeth RamÃrez-Salinas, Marco A. Velasco-Velázquez, Bettina Sommer,