The effect of triamterene on myocardial phosphodiesterase and adenylate cyclase.
The study concerned the effect of triamterene (TA) and its phase-II metabolite p-hydroxytriamterene-sulphuric acid ester (OH-TA ester) on myocardial phosphodiesterase (PDE) and adenylate cyclase (AC): (1) TA and OH-TA ester exerted a concentration-dependent inhibition of PDE. The estimated IC50 values of 127 and 72 mumol/l were 16 and 9 times higher than that of papaverine with 8 mumol/l. At comparable concentrations, TA produced its inotropic effect (EC50 96 mumol/l) in isolated guinea-pig atria so that PDE inhibition may well account for its pharmacodynamic action. (2) In isolated guinea-pig atria, the cyclic AMP content increased significantly with 15-30 s after the addition of TA and remained increased over a period of 15 min. This increase preceded the positive inotropic action, which reached its maximum after 5-10 min. (3) TA did not affect the basal activity of myocardial AC preparations. AC activation by isoprenaline (30 mumol/l) was, however, strongly inhibited.
D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000378:metabolism*; D000262:Adenylyl Cyclases / Q000378:metabolism*; D000818:Animals; D006168:Guinea Pigs; D006325:Heart Atria / Q000187:drug effects / Q000378:metabolism; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D009206:Myocardium / Q000201:enzymology*; D014223:Triamterene / Q000031:analogs & derivatives / Q000494:pharmacology*
C026475:hydroxytriamterene sulfate ester; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D000262:Adenylyl Cyclases; D007545:Isoproterenol; D014223:Triamterene