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 (h 5-HT1B) receptor sites in stably transfected Chinese hamster ovary (CH O-K1) cells. 2. Amiloride, free of intrinsic activity (pEC(50)<3.0), c ompetitively antagonized the sumatriptan-mediated inhibition (pEC(50): 7.37) of 100 mu M forskolin-induced cAMP formation with a pA(2) value of 4.46. 3. The antagonist feature was not shared by the amiloride de rivative ethylisopropylamiloride, not-withstanding a slightly higher 5 'HT1B receptor-binding affinity (pK(i): 4.87) than that of amiloride ( pK(i): 4.70). (C) 1997 Elsevier Science Inc.