Sex steroids effects on guinea pig airway smooth muscle tone and intracellular Ca2+ basal levels

• Published in: Molecular and cellular endocrinology Vol. 439; pp. 444 - 456
• Main Authors: Flores-Soto, Edgar, Reyes-García, Jorge, Carbajal-García, Abril, Campuzano-González, Elías, Perusquía, Mercedes, Sommer, Bettina, Montaño, Luis M.
• Format: Journal Article
• Language: English
• Published: Elsevier B.V 05.01.2017
• Subjects: 17β-estradiol; Canonical transient receptor potential 3 channel; Dehydroepiandrosterone; L-type Ca2+ channels; Store operated Ca2+ channels; Testosterone; Testosterone; Dehydroepiandrosterone; 17β-estradiol; Canonical transient receptor potential 3 channel; L-type Ca2+ channels; Store operated Ca2+ channels
• ISSN: 0303-7207; 1872-8057
• DOI: 10.1016/j.mce.2016.10.004

Testosterone (TES), other androgens and female sex steroids induce non-genomic rapid relaxing effects in airway smooth muscle (ASM). In guinea pig ASM, basal tension was relaxed by dehydroepiandrosterone (DHEA) and TES; 17β-estradiol (E2) had a small effect. Blockers of L-type voltage dependent Ca2+ channel (L-VDCC, D-600) and store operated Ca2+ channel (SOC, 2-APB) also relaxed the basal tone. In tracheal myocytes, DHEA and TES diminished intracellular basal Ca2+ concentrations (b[Ca2+]i) as D-600+2-APB but to a higher extend. TES after D-600+2APB or Pyr3, a blocker of canonical transient receptor potential 3 (TRPC3), further decreased b[Ca2+]i rendering this response equal to TES alone. With indomethacin, the b[Ca2+]i decrease induced by the blockade of L-VDCC and TRPC3 was not changed by the addition of TES. PGE2 or forskolin addition after D600+2-APB, decreased b[Ca2+]i resembling TES response. An adenylate cyclase inhibitor followed by D-600+2-APB lowered b[Ca2+]i, TES showed no further effect. Carbachol-induced [Ca2+]i increment was reduced by TES or DHEA. 17β-estradiol diminished KCl-induced contraction and, in tracheal myocytes, the voltage-dependent inward Ca2+ current. Conclusion: DHEA and TES diminish ASM tone and b[Ca2+]i by blocking L-VDCC and probably a constitutively active TRPC3, and by PGE2 synthesis. E2 lowers ASM basal tone by blocking only L-VDCC. •Dehydroepiandrosterone and testosterone reduce airway smooth muscle tone and b[Ca2+]i.•17β-estradiol barely reduces tracheal basal tone.•L-VDCC and TRPC3 channels are involved in TES-induced effects.•Only L-VDCC is involved in 17β-estradiol effects.•Airway smooth muscle tone and b[Ca2+]i are maintained by L-VDCC and TRPC3 channels.