PHOSPHODIESTERASE INHIBITION IN VENTRICULAR CARDIOMYOCYTES FROM GUINEA-PIG HEARTS

被引:30
作者
BETHKE, T
MEYER, W
SCHMITZ, W
SCHOLZ, H
STEIN, B
THOMAS, K
WENZLAFF, H
机构
[1] Abteilung Allgemeine Pharmakologie, Universitäts-Krankenhaus Eppendorf, Universität Hamburg, Hamburg, W-2000
关键词
PHOSPHODIESTERASES; VENTRICULAR CARDIOMYOCYTES; MULTICELLULAR VENTRICULAR TISSUE; GUINEA-PIG HEART; PDE INHIBITORS;
D O I
10.1111/j.1476-5381.1992.tb14474.x
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
1 The present study compared the cyclic nucleotide phosphodiesterase (PDE) activities in cardiomyocytes and ventricular cardiac tissue from guinea-pigs. The aim of the study was to determine whether PDE activities in ventricular tissue accurately reflect the isoenzymes present in cardiomyocytes. 2 In homogenates of cardiomyocytes and multicellular ventricular tissue, four distinct soluble PDE activities could be separated by DEAE-sepharose chromatography. 3 In multicellular cardiac tissue as well as in cardiomyocyte preparations, adenosine 3':5'-cyclic monophosphate (cyclic AMP) PDE isoenzymes I-IV were comparable in terms of substrate affinities, and inhibition or stimulation by guanosine 3':5'-cyclic monophosphate (cyclic GMP). However, in cardiomyocytes the V(max) values of PDE I-IV were lower by a factor of about 2 to 7 and the basal activities were lower by a factor of about 3 to 5 as compared to multicellular cardiac tissue. 4 To investigate whether the PDE I-IV activities were similarly inhibited by PDE inhibitors in both preparations, we studied the effects of 3-isobutyl-1-methylxanthine (IBMX), UD-CG 212 Cl (2-(4-hydroxy-phenyl)-5-(5-methyl-3-oxo-4,5-dihydro-2H-6-pyridazinyl)benzimidazole HCI) and rolipram. UD-CG 212 Cl was a selective PDE III inhibitor in cardiomyocytes (IC50 0.3-mu-mol 1(-1)) and in ventricular tissue (IC50 value 0.1-mu-mol 1(-1)). Rolipram selectively inhibited PDE IV in cardiomyocytes (IC50 1.4-mu-mol ml-1) and in ventricular tissue (IC50 1.1-mu-mol 1(-1)) whereas IBMX was a nonselective PDE inhibitor in both preparations. 5 It is concluded that the PDE isoenzymes I-IV from multicellular ventricular tissue can be used as a representative system for investigating PDE inhibiting properties of PDE inhibitors in the myocardium since comparable PDE isoenzymes I-IV exist in guinea-pig ventricular cardiomyocytes and multicellular ventricular tissue.
引用
收藏
页码:127 / 133
页数:7
相关论文
共 35 条
  • [31] MECHANISM UNDERLYING THE REDUCED POSITIVE INOTROPIC EFFECTS OF THE PHOSPHODIESTERASE-III INHIBITORS PIMOBENDAN, ADIBENDAN AND SATERINONE IN FAILING AS COMPARED TO NONFAILING HUMAN CARDIAC-MUSCLE PREPARATIONS
    VONDERLEYEN, H
    MENDE, U
    MEYER, W
    NEUMANN, J
    NOSE, M
    SCHMITZ, W
    SCHOLZ, H
    STARBATTY, J
    STEIN, B
    WENZLAFF, H
    DORING, V
    KALMAR, P
    HAVERICH, A
    [J]. NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY, 1991, 344 (01) : 90 - 100
  • [32] VONDERLEYEN H, 1989, KLIN WOCHENSCHR, V67, P605
  • [33] SUBCLASSES OF CYCLIC AMP-SPECIFIC PHOSPHODIESTERASE IN LEFT-VENTRICULAR MUSCLE AND THEIR INVOLVEMENT IN REGULATING MYOCARDIAL-CONTRACTILITY
    WEISHAAR, RE
    KOBYLARZSINGER, DC
    STEFFEN, RP
    KAPLAN, HR
    [J]. CIRCULATION RESEARCH, 1987, 61 (04) : 539 - 547
  • [34] MULTIPLE MOLECULAR-FORMS OF CYCLIC-NUCLEOTIDE PHOSPHODIESTERASE IN CARDIAC AND SMOOTH-MUSCLE AND IN PLATELETS - ISOLATION, CHARACTERIZATION, AND EFFECTS OF VARIOUS REFERENCE PHOSPHODIESTERASE INHIBITORS AND CARDIOTONIC AGENTS
    WEISHAAR, RE
    BURROWS, SD
    KOBYLARZ, DC
    QUADE, MM
    EVANS, DB
    [J]. BIOCHEMICAL PHARMACOLOGY, 1986, 35 (05) : 787 - 800
  • [35] INOTROPIC AND VASODILATOR EFFECTS OF AMRINONE ON ISOLATED HUMAN-TISSUE
    WILMSHURST, PT
    WALKER, JM
    FRY, CH
    MOUNSEY, JP
    TWORT, CHC
    WILLIAMS, BT
    DAVIES, MJ
    WEBBPEPLOE, MM
    [J]. CARDIOVASCULAR RESEARCH, 1984, 18 (05) : 302 - 309