Relaxant actions of viprostol and prostaglandin E2 on tracheal muscle and their effects on calcium influx

• Published in: Prostaglandins Vol. 36; no. 1; pp. 115 - 123
• Main Authors: Lai, F M, Cobuzzi, A, Tanikella, T, Cervoni, P
• Format: Journal Article
• Language: English
• Published: United States 01.07.1988
• Subjects: Animals; Calcium - metabolism; Calcium Chloride - pharmacology; Carbachol - pharmacology; Dinoprostone - analogs & derivatives; Dinoprostone - pharmacology; Guinea Pigs; Isoproterenol - pharmacology; Macaca fascicularis; Male; Muscle Contraction - drug effects; Muscle Relaxation - drug effects; Trachea - drug effects; Trachea - metabolism; Verapamil - pharmacology
• ISSN: 0090-6980
• DOI: 10.1016/0090-6980(88)90107-4

The relaxant effect of viprostol was studied in monkey and guinea-pig tracheal muscle rings in vitro and compared to that of prostaglandin E2 (PGE2), isoproterenol (ISO) and verapamil (guinea-pig trachea only). Viprostol, PGE2, ISO and verapamil produced a concentration-dependent relaxation of carbachol-contracted tracheal preparations. The rank order of potency in monkey trachea was viprostol = ISO greater than PGE2, while in guinea-pig treachea it was ISO greater than viprostol greater than PGE2 greater than verapamil. The relaxant effect of viprostol or PGE2 was not antagonized by propranolol, suggesting that beta-adrenoceptors are not involved. Epithelium removal did not affect the bronchorelaxant effects of viprostol, PGE2 or ISO. In K+-rich, Ca++-free Krebs solution, preincubation with an IC30 of verapamil antagonized CaCl2-induced contractions while an IC30 of viprostol, PGE2 or ISO did not. Preincubation with an IC90 of viprostol, PGE2 or ISO produced 0.5, 0.5 and 1.0 log unit shifts to the right of the CaCl2 concentration response curves, respectively. At this concentration, viprostol did not reduce the maximum effect of CaCl2, but PGE2 and ISO reduced it approximately 20%. However, preincubation with an IC90 of verapamil completely abolished the CaCl2 contraction. In conclusion, viprostol is a potent bronchodilator whose effect does not depend on the epithelium, beta-adrenoceptors or antagonism of Ca++ influx. Whether the bronchodilator effect of viprostol is via intracellular sequestration of calcium as that of PGE2 remains to be studied.