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).
Pauwels
P J
PJ
Centre de Recherche Pierre Fabre, Laboratory of Cellular and Molecular Neurobiology, Castres, France.
D000584:Amiloride / Q000494:pharmacology*; D000818:Animals; D001667:Binding, Competitive / Q000187:drug effects; D016466:CHO Cells; D005576:Colforsin / Q000494:pharmacology; D006224:Cricetinae; D000242:Cyclic AMP / Q000096:biosynthesis; D004232:Diuretics / Q000494:pharmacology*; D006168:Guinea Pigs; D011985:Receptors, Serotonin / Q000187:drug effects*; D012702:Serotonin Antagonists / Q000494:pharmacology*; D018170:Sumatriptan / Q000494:pharmacology
D004232:Diuretics; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D005576:Colforsin; D000584:Amiloride; D018170:Sumatriptan; D000242:Cyclic AMP