title: Changes in cyclic nucleotide phosphodiesterase activity and calmodulin concentration in heart muscle of cardiomyopathic hamsters.
abstract: Cyclic nucleotides (cAMP and cGMP) phosphodiesterase (PDE) activities and expression are altered in the cardiac muscle of cardiomyopathic heart failure, and PDE inhibitors improve the abnormal muscle condition through changing the cyclic nucleotide concentration. These observations prompted us to investigate the role of calmodulin (CaM) in the regulation of cyclic nucleotide PDE activities, and moreover to study the modulation of the PDE isozymes in heart failure, using cardiac muscles of cardiomyopathic hamster. The CaM concentrations in the heart muscle of the normal control and cardiomyopathic hamsters (each of three to four hamsters) varied with cell fraction and with the age of the animal. The CaM concentrations in the soluble fraction obtained from cardiomyopathic hamster tissue were significantly increased at 25 and 32 weeks of age (2.02 +/- 0.62 microg/mg protein (mean +/- S.E.), and 3.21 +/- 0.95) compared with that obtained from the control (0.60 +/- 0.04) or cardiomyopathic (0.95 +/- 0.12) hamsters at 8 weeks of age. The solubilized PDE isolated from the hamster heart muscle (three or four hamsters in each age) by column chromatography on diethylaminoethyl (DEAE)-cellulose revealed three peaks of activity, which may correspond to the isozymes of PDE classified recently, namely PDE I, II, and III. These three peaks of activity, particularly peak III, seen in the soluble fraction of cardiomyopathic hamster heart declined in proportion to the age of the animal compared with that of the control hamster heart. In the cGMP-PDE assay system, the concentration of CaM inhibitor W-7 required for 50% inhibition (IC(50)) of PDE I, II, and III peak activities was 140, 29, and 46 microM, respectively, suggesting that PDE II is more sensitive to W-7. These results suggest that alteration in these isozyme activities accompanied with changes of CaM concentration may influence the cardiac muscle contractility in cardiomyopathic hamster via changes of cyclic nucleotide concentration.
authors.affiliation: Department of Internal Medicine, Fujita Health University School of Medicine, Toyoake, Aichi 470 1192, Japan.
authors.forename: Rumi
authors.initials: R
authors.lastname: Masunaga
authors.forename: Akio
authors.initials: A
authors.lastname: Nagasaka
authors.forename: Yoshikuni
authors.initials: Y
authors.lastname: Sawai
authors.forename: Nobuki
authors.initials: N
authors.lastname: Hayakawa
authors.forename: Akira
authors.initials: A
authors.lastname: Nakai
authors.forename: Keiko
authors.initials: K
authors.lastname: Hotta
authors.forename: Yasuchika
authors.initials: Y
authors.lastname: Kato
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Hishida
authors.forename: Hisahide
authors.initials: H
authors.lastname: Takahashi
authors.forename: Michiko
authors.initials: M
authors.lastname: Naka
authors.forename: Yasuhito
authors.initials: Y
authors.lastname: Shimada
authors.forename: Toshio
authors.initials: T
authors.lastname: Tanaka
authors.forename: Hiroyoshi
authors.initials: H
authors.lastname: Hidaka
authors.forename: Mitsuyasu
authors.initials: M
authors.lastname: Itoh
mesh_terms: D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000096:biosynthesis*; D000367:Age Factors; D000818:Animals; D002147:Calmodulin / Q000378:metabolism*; D009202:Cardiomyopathies / Q000150:complications / Q000378:metabolism* / Q000473:pathology; D006224:Cricetinae; D005786:Gene Expression Regulation; D006333:Heart Failure / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D007527:Isoenzymes / Q000096:biosynthesis; D009200:Myocardial Contraction; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology
chemical_list: D002147:Calmodulin; D007527:Isoenzymes; D015105:3',5'-Cyclic-AMP Phosphodiesterases