PHOSPHODIESTERASE INHIBITION IN VENTRICULAR CARDIOMYOCYTES FROM GUINEA-PIG HEARTS
PHOSPHODIESTERASE INHIBITION IN VENTRICULAR CARDIOMYOCYTES FROM GUINEA-PIG HEARTS
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DOI：
10.1111/j.1476-5381.1992.tb14474.x
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发表时间：
1992-09-01
影响因子：
7.3
通讯作者：
WENZLAFF, H
中科院分区：
文献类型：
--
作者：
BETHKE, T;MEYER, W;WENZLAFF, H
1比较了豚鼠心肌细胞和心室组织环核苷酸磷酸二酯酶（PDE）的活性。该研究的目的是确定心室组织中PDE活性是否准确反映心肌细胞中存在的同工酶。2在心肌细胞和多细胞心室组织的匀浆中，可以通过DEAE-Sepharose色谱法分离出四种不同的可溶性PDE活性。3在多细胞心脏组织以及心肌细胞制备物中，腺苷3 '：5 '-环一磷酸（环AMP）PDE同工酶I-IV在底物亲和力和鸟苷3'：5 '-环一磷酸（环GMP）的抑制或刺激方面相当。然而，在心肌细胞中，PDE I-IV的V（max）值比多细胞心脏组织低约2至7倍，基础活性比多细胞心脏组织低约3至5倍。4为了研究PDE I-IV活性是否在两种制剂中被PDE抑制剂类似地抑制，我们研究了3-异丁基-1-甲基黄嘌呤（IBMX）的作用，UD-CG 212 Cl（2-（4-羟基-苯基）-5-（5-甲基-3-氧代-4，5-二氢-2H-6-哒嗪基）苯并咪唑HCl）和咯利普兰。UD-CG 212 Cl是心肌细胞（IC 50 0.3 μ mol 1（-1））和心室组织（IC 50值0.1 μ mol 1（-1））中的选择性PDE III抑制剂。咯利普兰选择性抑制心肌细胞PDE IV（IC 50 1.4 μ mol ml-1）和心室组织中（IC 50 1.1 μ mol 1（-1）），而IBMX在两种情况下均为非选择性PDE抑制剂。5可以得出结论，PDE同工酶I-来自多细胞心室组织的IV可用作研究心肌中PDE抑制剂的PDE抑制性质的代表性系统，可比较的PDE同工酶I-IV存在于豚鼠心室心肌细胞和多细胞心室组织中。
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.