RT Journal Article
SR Electronic
T1 Testosterone concentration-dependent effects on airway smooth muscle
JF European Respiratory Journal
JO Eur Respir J
FD European Respiratory Society
SP PA4069
DO 10.1183/13993003.congress-2019.PA4069
VO 54
IS suppl 63
A1 Bettina Sommer
A1 Edgar Flores-Soto
A1 Jorge Reyes-García
A1 Verónica Díaz-Hernández
A1 Abril Carbajal-García
A1 Luis M Montaño-Ramírez
YR 2019
UL http://erj.ersjournals.com/content/54/suppl_63/PA4069.abstract
AB Steroid sex hormones play an important role in airway ailments such as asthma. This illness affects boys rather than girls during infancy and this proportion radically reverses in puberty. Conceivably, plasmatic androgen concentration in young men increases at this age and might be related to lower airway hyperresponsiveness. Meanwhile, androgens´ addition to pre-contracted airway smooth muscle (ASM) in vitro, concentration-dependently relaxes them. We therefore hypothesized that androgens might exert their concentration dependent effects on ASM through different cellular mechanisms. To study physiological testosterone (TES) concentrations (10 nM) effects on ASM, we tested its effects on carbachol (CCh)-induced intracellular Ca2+ concentration ([Ca2+]i) increment and found that CCh Ca2+ response was abolished. In turn, ATP-induced [Ca2+]i increment was partially blocked by TES. We confirmed that only P2Y (metabotropic) receptors were altered by TES; while this androgen showed no effect on histamine [Ca2+]i increase. These results indicated that the PLC-IP3 signaling pathway is involved. Studies using photolysis of caged-IP3 confirmed this hypothesis. At supraphysiological concentrations (µM), TES concentration-dependently (10, 32, 100, and 178 μM) relaxed CCh pre-contracted ASM in vitro by blocking L-type voltage dependent Ca2+channels (VDCC) and store operated Ca2+ channels (SOCC). A role for PGE2 in this TES-induced relaxation was also established. In conclusion, μM TES concentrations decrease ASM [Ca2+]i by blocking VDCC and SOCC and stimulating PGE2 synthesis; while nM concentrations reduce [Ca2+]i increases induced by CCh and ATP, by hindering IP3 receptor functioning.FootnotesCite this article as: European Respiratory Journal 2019; 54: Suppl. 63, PA4069.This is an ERS International Congress abstract. No full-text version is available. Further material to accompany this abstract may be available at www.ers-education.org (ERS member access only).