Relaxant actions of PGE2 and its derivative (YPG-209) on canine tracheal smooth muscle and their enhancement of Ca++ uptake by the microsomal fraction.

Abstract

The spasmogenic action of tetraethylammonium on cvanine tracheal smooth muscle was dependent on the extracellular Ca2+ concentration. Acetylcholine produced partial contraction for a certain period of time after removal of extracellular Ca2+, suggesting the release of Ca2+ from intracellular Ca2+ stores into the cytosol. PG[prostaglandin]E2, 16(S)-methyl-20-methoxy-PGE2 (YPG-209), verapamil and dibutyryl cAMP relaxed the acetylcholine-induced contraction of the trachea. Pretreatment with PG or dibutyryl cAMP more efficiently suppressed acetylcholine-induced contraction, i.e., verapamil blocked the spasmogenic action of tetraethylammonium in a relatively selective manner. The PG and dibutyryl cAMP inhibited the spasmogenic action of acetylcholine in a Ca2+-free medium. Influx of 45Ca into tracheal smooth muscle which was produced by 83 mM KCl plus 20 mM tetraethylammonium was not significantly affected by PG as measured by the La method. PGE2 increased ATP-dependent Ca2+ uptake by the microsomes from tracheal smooth muscle. PG may induce relaxation of the airway smooth muscle mainly through affecting the intracellular Ca2+ movement by enhancement of sequestration of Ca2+ to the microsomes.