The effect of azelastine and some other antiasthmatic and antiallergic drugs on calmodulin and protein kinase C.
The antiallergic and antiasthmatic drug, azelastine, interacts strongly with calmodulin (but not bovine serum albumin) as determined by an indirect assay; it also moderately inhibited the Ca2+-calmodulin-dependent enzyme bovine brain phosphodiesterase. Ketotifen was less active than azelastine in both assays of calmodulin reactivity and both drugs were less active than the recognized calmodulin inhibitor, W-7. Neither azelastine nor ketotifen had any inhibitory effect on the Ca2+- and phospholipid-dependent protein kinase C. A number of other commonly employed antiallergic and antiasthmatic drugs were essentially inactive in the calmodulin assays and had no or marginal inhibitory effect on protein kinase C.
Middleton
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E
Department of Medicine State University of New York, Buffalo 14214.
Ferriola
P
P
Drzewiecki
G
G
Sofia
R D
RD
D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000037:antagonists & inhibitors; D000818:Animals; D001921:Brain / Q000201:enzymology; D002118:Calcium / Q000494:pharmacology; D002147:Calmodulin / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D005456:Fluorescent Dyes; D006634:Histamine H1 Antagonists / Q000494:pharmacology*; D007665:Ketotifen / Q000494:pharmacology; D010726:Phosphodiesterase Inhibitors; D010793:Phthalazines / Q000494:pharmacology*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors*; D011724:Pyridazines / Q000494:pharmacology*; D051381:Rats; D012710:Serum Albumin, Bovine / Q000378:metabolism; D013050:Spectrometry, Fluorescence; D013449:Sulfonamides / Q000494:pharmacology
D002147:Calmodulin; D005456:Fluorescent Dyes; D006634:Histamine H1 Antagonists; D010726:Phosphodiesterase Inhibitors; D010793:Phthalazines; D011724:Pyridazines; D013449:Sulfonamides; D012710:Serum Albumin, Bovine; C017967:W 7; D011493:Protein Kinase C; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D002118:Calcium; D007665:Ketotifen; C020976:azelastine