Calmodulin and protein kinase C antagonists also inhibit the Ca2+-dependent protein protease, calpain I.
The calmodulin and C-kinase antagonists melittin, calmidazolium, N-(6-aminohexyl)-5-chloro-1-napthalenesulfonamide (W7), and trifluoperazine (TFP) also inhibit the activity of the human erythrocyte Ca2+-dependent protease, calpain I. W-5, the nonchlorinated derivative of W-7, was ineffective as an inhibitor of calpain I just as it is for calmodulin and protein kinase C. Dose response studies provided the following IC50 values: melittin, 2.6 microM; calmidazolium, 6.2 microM; trifluoperazine, 130 microM; W-7, 251 microM. These IC50 values indicate that the compounds have affinities 10 to 600 fold less for calpain I than for calmodulin; however, the affinities of the inhibitory compounds are comparable for calpain I and protein kinase C. Kinetic analysis indicates that the compounds are competitive inhibitors of calpain I with respect to substrate.
Brumley
L M
LM
Department of Pharmacology, University of Alabama, Birmingham 35294.
Wallace
R W
RW
D001514:Bee Venoms / Q000494:pharmacology*; D002147:Calmodulin / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D002154:Calpain / Q000037:antagonists & inhibitors / Q000097:blood*; D004912:Erythrocytes / Q000201:enzymology*; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology*; D007700:Kinetics; D008555:Melitten / Q000494:pharmacology*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors*; D013449:Sulfonamides / Q000494:pharmacology*; D014268:Trifluoperazine / Q000494:pharmacology*
D001514:Bee Venoms; D002147:Calmodulin; D007093:Imidazoles; D013449:Sulfonamides; D008555:Melitten; D014268:Trifluoperazine; C031938:calmidazolium; C017967:W 7; D011493:Protein Kinase C; D002154:Calpain