Inhibition of calmodulin dependent c-AMP-phosphodiesterase by moxaverine and papaverine.
Vasodilator properties of papaverine and moxaverine have been attributed to an inhibition of cyclic adenosine monophosphate (c-AMP) phosphodiesterase (PDE). The discovery of the calmodulin (CaM) dependence of c-AMP PDE activity necessitates a reinvestigation of the molecular mode of action of papaverine-like compounds. Separately analyzing the inhibition of basal and CaM-stimulated enzyme activity by these drugs proves the preferred inhibition of the CaM stimulated c-AMP PDE. Lipophilicity is assumed to represent an indicator of CaM-inhibitory potency.
Mannhold
R
R
Department of Clinical Physiology, University of Düsseldorf, Fed. Rep. of Germany.
D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000037:antagonists & inhibitors*; D000818:Animals; D002147:Calmodulin / Q000302:isolation & purification / Q000378:metabolism*; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D002642:Chick Embryo; D054677:Cyclic Nucleotide Phosphodiesterases, Type 1; D008055:Lipids / Q000032:analysis; D010208:Papaverine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D010276:Parasympatholytics / Q000494:pharmacology*; D012995:Solubility
D002147:Calmodulin; D008055:Lipids; D010276:Parasympatholytics; D010208:Papaverine; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D054677:Cyclic Nucleotide Phosphodiesterases, Type 1; C004490:moxaverine