Actions of amiloride analogues on prostacyclin synthesis by rat aortic rings.
1 Fresh rat aortic rings were incubated in HEPES-buffered salt solutions (pH 8.0) in the presence or absence of amiloride analogues. The effect of these drugs on prostacyclin (PGI2) synthesis was determined by radioimmunoassay of the stable hydrolysis product 6-oxo-prostaglandin (PG)F1 alpha. 2 Amiloride and phenamil (potent inhibitors of epithelial Na+ transport) had no significant effect on basal or Ca2+-stimulated PGI2 synthesis. 3 Several analogues previously reported to inhibit Na+/Ca2+ exchange caused a dose-related increase in 6-oxo-PGF1 alpha production in media containing NaCl 120 mM and CaCl2 2.5 mM. 2',3'-Benzobenzamil was the most potent analogue with a maximum stimulation of 4.51 +/- 0.89 fold, and an EC50 of 3 x 10(-5) M. 4 Amiloride analogues bearing substituents on the 5-amino group of the pyrazine ring have been reported to inhibit Na+/H+ exchange more potently than Na+/Ca2+ exchange. Three of these compounds inhibited Ca2+-stimulated 6-oxo-PGF1 alpha production at concentrations that did not significantly influence basal 6-oxo-PGF1 alpha production.
Ritter
J M
JM
Department of Clinical Pharmacology, Royal Postgraduate Medical School, London.
Aksoy
A
A
Cragoe
E J
EJ
Taylor
G W
GW
D015121:6-Ketoprostaglandin F1 alpha / Q000032:analysis; D000584:Amiloride / Q000031:analogs & derivatives / Q000494:pharmacology*; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000378:metabolism; D002118:Calcium / Q000494:pharmacology; D011464:Epoprostenol / Q000096:biosynthesis*; D066298:In Vitro Techniques; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism*; D011863:Radioimmunoassay; D051381:Rats
D015121:6-Ketoprostaglandin F1 alpha; D000584:Amiloride; D011464:Epoprostenol; D002118:Calcium