Delbridge L M, Stewart A G, Goulter C M, Morgan T O, Harris P J
Department of Physiology, University of Melbourne, Parkville, Victoria, Australia.
J Mol Cell Cardiol. 1994 Feb;26(2):185-93. doi: 10.1006/jmcc.1994.1021.
In various isolated cardiac tissue preparations the phospholipid mediator platelet-activating factor (PAF, 1-O-hexadecyl-2-acetyl-sn-glycero-3-phosphorylcholine) may elicit a positive, negative or no inotropic response. In the multicellular preparation it is difficult to differentiate and characterize the direct actions of PAF on the myocardium from the effects due to the release of secondary mediators from non-myocyte cell types. Thus in the present study the inotropic effects of PAF (10(-11), 10(-9), 10(-7) M) and a specific PAF receptor antagonist, WEB-2086, PAF receptor antagonist. WEB-2086, on the contractility of enzymatically isolated adult rat cardiomyocytes have been investigated. PAF (10(-7) M) reduced maximum cell shortening by 23% compared to the initial level, delayed excitation contraction coupling, abbreviated the contraction cycle and reduced the maximum rate of cell lengthening during relaxation. Lower concentrations of PAF elicited smaller negative inotropic responses. There was no evidence of a positive inotropic effect of PAF at any concentration tested or at any time after the onset of treatment. Co-treatment with WEB-2086 (10(-5) M) prevented the negative inotropic response to PAF. WEB-2086 alone increased maximum shortening by 16% compared to initial performance, extended the contraction cycle and increased the maximum rates of shortening and lengthening. WEB-2086 had no effect on excitation contraction coupling latency. The selective alteration of contraction parameters induced by PAF and WEB-2086 indicates that, in addition to antagonizing the negative inotropic action of exogenous PAF, WEB-2086 alone enhances contractility. These results demonstrate that PAF has a direct, receptor-mediated negative inotropic effect on adult contractility. These results demonstrate that PAF has a direct, receptor-mediated negative inotropic effect on adult cardiomyocytes.
在各种离体心脏组织制备物中，磷脂介质血小板活化因子（PAF，1-O-十六烷基-2-乙酰基-sn-甘油-3-磷酸胆碱）可能引发正性、负性或无变力反应。在多细胞制备物中，很难将PAF对心肌的直接作用与非心肌细胞类型释放的次级介质所产生的效应区分开来并进行表征。因此，在本研究中，研究了PAF（10⁻¹¹、10⁻⁹、10⁻⁷ M）和一种特异性PAF受体拮抗剂WEB-2086对酶分离的成年大鼠心肌细胞收缩性的影响。与初始水平相比，PAF（10⁻⁷ M）使最大细胞缩短减少了23%，延迟了兴奋-收缩偶联，缩短了收缩周期，并降低了舒张期细胞伸长的最大速率。较低浓度的PAF引起较小的负性变力反应。在任何测试浓度或治疗开始后的任何时间，均未发现PAF有正性变力作用的证据。与WEB-2086（10⁻⁵ M）共同处理可防止对PAF的负性变力反应。与初始性能相比，单独使用WEB-2086可使最大缩短增加16%，延长收缩周期，并增加缩短和伸长的最大速率。WEB-2086对兴奋-收缩偶联潜伏期没有影响。PAF和WEB-2086诱导的收缩参数的选择性改变表明，除了拮抗外源性PAF的负性变力作用外，单独使用WEB-2086可增强收缩性。这些结果表明，PAF对成年心肌细胞具有直接的、受体介导的负性变力作用。
