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

Abstract

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.

Keywords: 17β-estradiol; Canonical transient receptor potential 3 channel; Dehydroepiandrosterone; L-type Ca(2+) channels; Store operated Ca(2+) channels; Testosterone.