Relaxant actions of PGE2 and its derivative (YPG-209) on canine tracheal smooth muscle and their enhancement of Ca++ uptake by the microsomal fraction.
The spasmogenic action of tetraethylammonium on canine tracheal smooth muscle was dependent on the extracellular Ca++ concentration. Acetylcholine, on the contrary, produced partial contraction for a certain period of time after removal of extracellular Ca++, suggesting the release of Ca++ from intracellular Ca++ stores into the cytosol. PGE2, 16(S)-methyl-20-methoxy-PGE2 (YPG-209), verapamil, and dibutyryl cyclic AMP relaxed the acetylcholine-induced contraction of the trachea. Pretreatment with prostaglandins or dibutyryl cyclic AMP more efficiently suppressed acetylcholine-induced contraction, whereas verapamil blocked the spasmogenic action of tetraethylammonium in a relatively selective manner. The prostaglandins and dibutyryl cyclic AMP also inhibited the spasmogenic action of acetylcholine in a Ca++-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 prostaglandins as measured by the lanthanum method. In addition, PGE2 increased ATP-dependent Ca++ uptake by the microsomes from tracheal smooth muscle. These results suggest that prostaglandins induce relaxation of the airway smooth muscle mainly through affecting the intracellular Ca++ movement such as by enhancement of sequestration of Ca++ to the microsomes.
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002132:Calcium Radioisotopes; D015232:Dinoprostone / Q000031:analogs & derivatives; D004285:Dogs; D005260:Female; D008297:Male; D008861:Microsomes / Q000378:metabolism*; D009119:Muscle Contraction / Q000187:drug effects; D009125:Muscle Relaxants, Central; D009130:Muscle, Smooth / Q000187:drug effects* / Q000378:metabolism; D011458:Prostaglandins E / Q000494:pharmacology*; D011459:Prostaglandins E, Synthetic / Q000494:pharmacology*; D014132:Trachea / Q000378:metabolism
D002132:Calcium Radioisotopes; D009125:Muscle Relaxants, Central; D011458:Prostaglandins E; D011459:Prostaglandins E, Synthetic; C026720:16-methyl-20-methoxy-PGE2; D015232:Dinoprostone; D002118:Calcium