Competitive and silent antagonism of recombinant 5-HT1B receptors by amiloride

1. The cyclic adenosine monophosphate (cAMP) response of the diuretic amiloride was compared with sumatriptan at recombinant human 5-HT1B (h5-HT1B) receptor sites in stably transfected Chinese hamster ovary (CHO-K1) cells. 2. Amiloride, free of intrinsic activity (pEC50 < 3.0), competitively antagonized the sumatriptan-mediated inhibition (pEC50: 7.37) of 100 microM forskolin-induced cAMP formation with a pA2 value of 4.46. 3. The antagonist feature was not shared by the amiloride derivative ethylisopropylamiloride, notwithstanding a slightly higher 5-HT1B receptor-binding affinity (pKi: 4.87) than that of amiloride (pKi: 4.70).