Schlüter K D, Piper H M
Physiologisches Institut I, Universität Düsseldorf, Federal Republic of Germany.
Am J Physiol. 1992 Dec;263(6 Pt 2):H1739-46. doi: 10.1152/ajpheart.1992.263.6.H1739.
Trophic effects of isoproterenol (Iso), norepinephrine (NE), phenylephrine (PE), and biologically active fragments of parathyroid hormone (PTH), PTH-(1-34) and PTH-(28-48), were investigated in mechanically quiescent, isolated ventricular cardiomyocytes from adult rat. In 24-h incubations in modified serum-free medium 199 incorporation of [14C]phenylalanine, changes in total protein and specific activities of cytosolic enzymes, creatine kinase (CK) and lactate dehydrogenase (LDH) were monitored. NE and PE (10 microM), but not Iso, distinctly increased phenylalanine incorporation, total cell protein, and specific activity of CK but not LDH. Induction of CK, but not LDH, was also produced by phorbol 12-myristate 13-acetate (10 nM) but not dibutyryl adenosine 3',5'-cyclic monophosphate (DBcAMP, 1 mM). It was abolished by copresence of cycloheximide (35 microM) or actinomycin D (5 microM). CK-BB was the only induced isoform of CK, as shown for PE incubations. PTH-(1-34) and PTH-(28-48) (30-300 nM) had effects comparable to NE and PE. They increased phenylalanine incorporation and total protein content and induced CK but not LDH. In summary, distinct trophic effects on adult cardiomyocytes were found with alpha 1-adrenergic agonists, fragments of PTH containing the midregional amino acids 28-34, and direct activation of protein kinase C but neither beta-adrenergic agonists nor DBcAMP.
研究了异丙肾上腺素(Iso)、去甲肾上腺素(NE)、苯肾上腺素(PE)以及甲状旁腺激素(PTH)的生物活性片段PTH-(1-34)和PTH-(28-48)对成年大鼠机械性静止、分离的心室心肌细胞的营养作用。在改良的无血清培养基199中孵育24小时后,监测[14C]苯丙氨酸的掺入、总蛋白的变化以及细胞溶质酶肌酸激酶(CK)和乳酸脱氢酶(LDH)的比活性。NE和PE(10 microM)能显著增加苯丙氨酸掺入、总细胞蛋白以及CK的比活性,但对LDH无此作用,而Iso则无此效果。佛波醇12-肉豆蔻酸酯13-乙酸酯(10 nM)能诱导CK而不是LDH,二丁酰腺苷3',5'-环磷酸(DBcAMP,1 mM)则不能。放线菌酮(35 microM)或放线菌素D(5 microM)同时存在时可消除这种诱导作用。如PE孵育实验所示,CK-BB是唯一被诱导的CK同工型。PTH-(1-34)和PTH-(28-48)(30 - 300 nM)具有与NE和PE相当的作用。它们增加苯丙氨酸掺入和总蛋白含量,并诱导CK但不诱导LDH。总之,发现α1-肾上腺素能激动剂、含中部区域氨基酸28 - 34的PTH片段以及蛋白激酶C的直接激活对成年心肌细胞有明显的营养作用,而β-肾上腺素能激动剂和DBcAMP则无此作用。