Selective effect of phorbol ester on serotonin removal and ACE activity in rabbit lungs.
Selective effect of phorbol ester on serotonin removal and ACE activity in rabbit lungs.
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佛波酯对兔肺血清素去除和 ACE 活性的选择性影响。
DOI：
10.1152/jappl.1988.65.1.377
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发表时间：
1988
期刊：
影响因子：
--
通讯作者：
Pitt,BR
中科院分区：
文献类型：
--
作者：
Myers,CL;Pitt,BR
在离体兔肺原位灌注Krebs-白蛋白，观察佛波酯（PMA）对肺内5-[14 C]羟色胺（5-[14 C]HT）清除和血管紧张素转换酶（ACE）合成底物[~ 3 H]苯甲酰苯丙氨酰丙氨酰脯氨酸（BPAP）代谢的影响。在用80 nM PMA（n = 11）或PMA加133 μ M罂粟碱（n = 10）或PMA稀释剂（二甲基亚砜，n = 11）灌注之前、期间和之后评估代谢功能。器官动力学参数（表观Vmax，Km）计算通过使用指示剂稀释技术和全器官代谢的数学模型。PMA处理导致BPAP代谢的Vmax（从52 +/- 4至30 +/- 4 nmol/s）和5-HT去除（从2.1 +/- 0.2至1.1 +/- 0.1 nmol/s）显着下降。BPAP的Km没有显著改变，而5-HT去除的Km在治疗后更高（治疗前，1.1 +/- 0.1 μ M;治疗后，2.3 +/- 0.6 μ M）。用罂粟碱灌注，减弱了PMA的升压反应，消除了PMA诱导的BPAP代谢Vmax和5-HT清除Km的变化，但保留了PMA诱导的5-HT清除Vmax的变化。我们的结论是，PMA改变内皮代谢功能的血液动力学和生化机制是独立的循环血细胞。BPAP代谢的肺容量可能在很大程度上反映了灌注表面积，5-HT清除能力可能对该模型中的坦率内皮细胞功能障碍更敏感。
The effect of phorbol myristate acetate (PMA) on pulmonary removal of [14C]serotonin (5-[14C]HT) and metabolism of [3H]benzoyl-phenylalanyl-alanyl-proline (BPAP), a synthetic substrate for angiotensin-converting enzyme (ACE), was evaluated in isolated rabbit lungs perfused in situ with Krebs-albumin. Metabolic functions were assessed before, during, and after perfusion with 80 nM PMA (n = 11), or PMA plus 133 microM papaverine (n = 10) or PMA diluent (dimethyl sulfoxide, n = 11). Organ kinetic parameters (apparent Vmax, Km) were calculated by use of indicator-dilution techniques and by a mathematical model of whole-organ metabolism. PMA treatment resulted in a significant decline in Vmax for BPAP metabolism (from 52 +/- 4 to 30 +/- 4 nmol/s) and 5-HT removal (from 2.1 +/- 0.2 to 1.1 +/- 0.1 nmol/s). Km for BPAP was not significantly altered, whereas Km for 5-HT removal was higher after treatment (before treatment, 1.1 +/- 0.1 microM; after treatment, 2.3 +/- 0.6 microM). Coperfusion with papaverine, which attenuated the pressor response to PMA, abolished PMA-induced changes in Vmax for BPAP metabolism and in Km for 5-HT removal but left PMA-induced changes in Vmax for 5-HT removal intact. We conclude that PMA alters endothelial metabolic function by both hemodynamic and biochemical mechanisms that are independent of circulating blood cells. Pulmonary capacity for BPAP metabolism may largely reflect perfused surface area, and capacity for 5-HT removal may be more sensitive to frank endothelial cell dysfunction in this model.