Non‐genomic relaxation effect of testosterone through L‐type and store operated Ca2+ channels blockade in guinea pig airway smooth muscle (1174.2)

Abstract

In vascular smooth muscle, testosterone (TES) produces relaxation blocking L‐type Ca2+ channels. Recently, we found that L‐type and store operated (SOC) Ca2+ channels are the main membranal structures that provide extracellular Ca2+ for carbachol‐induced contraction in airway smooth muscle (ASM). Thus, we studied the possible interactions between L‐type and SOC channels in TES‐induced relaxation in guinea pig ASM. TES (10, 32 and 100 μM) induced a complete relaxation of Cch pre‐contracted tracheal smooth muscle and indomethacin partially inhibited this response. In single myocytes, the KCl induced intracellular Ca2+ increase ([Ca2+]i) was decreased by 32 and completely blocked by 100 nM TES. This androgen (32 and 100 μM) significantly diminished (~25 and 49 %, respectively) the capacitative Ca2+ entry. Myocytes stimulated with carbachol (Cch) produced a transient Ca2+ peak followed by a sustained plateau and 100 μM TES completely abolished the Cch induced Ca2+ plateau. Indomethacin, significantly diminished this effect of TES. When D‐600 was added during the plateau phase, a partial diminution (~35 %) was observed. A grater decrease (~78 %) was also seen when 2‐APB (SOC antagonist) was used. The combination of both drugs completely abolished the Ca2+ plateau induced by Cch. We concluded that TES blocks L‐type Ca2+ channels at nanomolar and SOC channels at micromolar concentration to induce relaxation.Grant Funding Source: PAPIIT‐DGAPA, UNAM IN200613