Inhibitory effect of sex steroids on guinea-pig airway smooth muscle contractions.

We assessed the possible inhibition of airway smooth muscle contraction by progesterone and pregnanolones (5 alpha and 5 beta-reduced). Progesterone and 5 beta-pregnanolone prevented histamine- or carbachol-induced contraction in isolated guinea-pig trachea and potency was related to their respective chemical structure; progesterone was the most potent inhibitor in a concentration-dependent manner. The steroids also exhibited calcium antagonist activities in this tissue as assessed by their action on calcium entry in depolarized preparations; this event involved the immediate blockade of the extracellular calcium influx in the muscle cell membrane, indicating a nongenomic action. Classical GABAA antagonists did not block the progesterone response, implying no involvement of the GABAA-receptor complex. Our results suggest a bronchodilating effect induced by sex steroids, and probably by other related compounds, before the genomic mechanisms take place. This nongenomic action of steroids could have potential therapeutic usefulness in the treatment of asthma.