Two types of calmodulin antagonists: a structurally related interaction.
The ability of several calmodulin (CaM) antagonists, such as N-(6-aminohexyl)-5-chloro-1-naphthalene sulfonamide (W-7) and trifluoperazine, to displace [3H]-W-7 from CaM correlated with the inhibition of Ca2+-CaM-dependent phosphodiesterase (PDE) by these agents. These antagonists also suppressed the increase in fluorescence of n-phenyl-1-naphthylamine (NPN) by complex formation with CaM in the presence of Ca2+. However, the ability of some CaM antagonists, such as prenylamine and butaclamol, to displace [3H]-W-7 from CaM did not correlate with the inhibition of Ca2+-PDE. These antagonists enhanced the increase in fluorescence of NPN by complex formation with CaM in the presence of Ca2+. In a study employing 1H-nuclear magnetic resonance, the spectrum changes of the aromatic region of CaM induced by prenylamine were significantly more marked than the changes induced by W-7. These findings suggest two types of CaM antagonists. The compounds in each of the groups appear to have common molecular structures.
D000818:Animals; D002147:Calmodulin / Q000037:antagonists & inhibitors*; D002417:Cattle; D004789:Enzyme Activation; D009682:Magnetic Resonance Spectroscopy; D009419:Nerve Tissue Proteins / Q000378:metabolism; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D010727:Phosphoric Diester Hydrolases / Q000378:metabolism; D011299:Prenylamine / Q000494:pharmacology; D011487:Protein Conformation; D013050:Spectrometry, Fluorescence; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000378:metabolism; D014268:Trifluoperazine / Q000494:pharmacology
D002147:Calmodulin; D009419:Nerve Tissue Proteins; D010726:Phosphodiesterase Inhibitors; D013449:Sulfonamides; D014268:Trifluoperazine; C017967:W 7; D010727:Phosphoric Diester Hydrolases; D011299:Prenylamine