Relaxation and inhibition of contractile response to electrical field stimulation by Beraprost sodium in canine airway smooth muscle.
To elucidate the effect of Beraprost, a stable prostaglandin (PG) I2 analogue, on airway smooth muscle functions and its mechanism of action, we studied canine bronchial segments under isometric conditions in vitro. Addition of PGI2 and its analogues dose-dependently relaxed bronchial smooth muscle precontracted with acetylcholine, with the rank order of potency being Beraprost (1) > or = Hoprost (0.65) > PGI2 (0.04), accompanied by the corresponding increase in intracellular cyclic AMP levels. The Beraprost- and PGI2-induced muscle relaxations were significantly inhibited by each of the PG antagonist diphloretin phosphate, the adenylate cyclase inhibitor SQ 22,536, and the Na(+)-K(+)-ATPase inhibitor ouabain. Beraprost and PGI2 at concentrations insufficient to cause muscle relaxation reduced the contractile responses to electrical field stimulation, whereas they were without effect on those to exogenous acetylcholine. These results suggest that Beraprost not only potently relaxes airway smooth muscle through cyclic AMP production and the subsequent stimulation of Na(+)-K(+)-ATPase but also reduces neurally mediated contraction by inhibiting the release of acetylcholine from the cholinergic nerve terminals.
First Department of Medicine, Tokyo Women's Medical College, Japan.
J
J
Tamaoki
A
A
Chiyotani
K
K
Takeyama
F
F
Yamauchi
E
E
Tagaya
K
K
Konno
D000109:Acetylcholine / Q000494:pharmacology; D000225:Adenine / Q000031:analogs & derivatives / Q000494:pharmacology; D000067956:Adenylyl Cyclase Inhibitors; D000818:Animals; D001980:Bronchi / Q000187:drug effects / Q000502:physiology*; D004285:Dogs; D004558:Electric Stimulation; D011464:Epoprostenol / Q000031:analogs & derivatives* / Q000494:pharmacology; D005260:Female; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009126:Muscle Relaxation / Q000187:drug effects*; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology*; D010042:Ouabain / Q000494:pharmacology; D011121:Polyphloretin Phosphate / Q000494:pharmacology; D011189:Potassium Chloride / Q000494:pharmacology; D011448:Prostaglandin Antagonists / Q000494:pharmacology; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors
D000067956:Adenylyl Cyclase Inhibitors; D011448:Prostaglandin Antagonists; C017759:9-(tetrahydro-2-furyl)-adenine; C048081:beraprost; C013509:diphloretin phosphate; D010042:Ouabain; D011189:Potassium Chloride; D011121:Polyphloretin Phosphate; D011464:Epoprostenol; D000254:Sodium-Potassium-Exchanging ATPase; D000225:Adenine; D000109:Acetylcholine