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

作者：Flores Soto Edgar; Reyes Garcia Jorge; Carbajal Garcia Abril; Campuzano Gonzalez Elias; Perusquia Mercedes; Sommer Bettina; Montano Luis M^*

来源：Molecular and Cellular Endocrinology, 2017, 439(C): 444-456.

DOI：10.1016/j.mce.2016.10.004

• L-type Ca2+ channels
• Store operated Ca2+ channels
• Canonical transient receptor potential 3 channel
• Testosterone
• Dehydroepiandrosterone
• 17 beta-estradiol

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; 17 beta-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. PGE(2) 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. Carbacho-linduced (b)[Ca2+](i); increment was reduced by TES or DHEA. 17 beta-estradiol diminished KCI-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 PGE(2) synthesis. E-2 lowers ASM basal tone by blocking only L-VDCC.

• 出版日期2017-1-5