INHIBITORY EFFECT OF SEX STEROIDS ON GUINEA-PIG AIRWAY SMOOTH-MUSCLE CONTRACTIONS

We assessed the possible inhibition of airway smooth muscle contractio n by progesterone and pregnanolones (5 alpha and 5 beta-reduced). Prog esterone and 5 beta-pregnanolone prevented histamine-or carbachol-indu ced contraction in isolated guinea-pig trachea and potency was related to their respective chemical structure; progesterone was the most pot ent inhibitor in a concentration-dependent manner. The steroids also e xhibited calcium antagonist activities in this tissue as assessed by t heir action on calcium entry in depolarized preparations; this event i nvolved the immediate blockade of the extracellular calcium influx in the muscle cell membrane, indicating a nongenomic action. Classical GA BA(A) antagonists did not block the progesterone response, implying no involvement of the GABA(A)-receptor complex. Our results suggest a br onchodilating effect induced by sex steroids, and probably by other re lated compounds, before the genomic mechanisms take place. This nongen omic action of steroids could have potential therapeutic usefulness in the treatment of asthma. (C) 1997 Elsevier Science Inc.