Ganey P E, Roth R A
Toxicol Appl Pharmacol. 1987 Apr;88(2):157-64. doi: 10.1016/0041-008x(87)90001-9.
Monocrotaline pyrrole (MCTP), a metabolite of the plant toxin monocrotaline, produces pulmonary vascular injury, pulmonary hypertension, and right ventricular enlargement (RVE) in rats by an unknown mechanism. A role for platelets has been suggested by the observation that antibody-induced thrombocytopenia reduces the RVE caused by MCTP. The platelet can release a number of vasoconstrictive agents, such as 5-hydroxytryptamine (5HT) and thromboxane A2 (TxA2), that could possibly contribute to pulmonary hypertension. It was of interest to determine whether treatment with MCTP alters platelet 5HT content or alters the release of TxA2 in platelet-rich plasma (PRP) in response to aggregation. Fourteen days following treatment with MCTP when pulmonary hypertension is well-established and RVE is present, the concentration of 5HT in washed platelets or in platelet-poor plasma was not different in treated and control rats. One day following treatment with MCTP, before lung injury is evident, the concentration of TxB2, a stable metabolite of TxA2, was higher in unstimulated PRP from treated rats than in control rats. The concentration of TxB2 was also examined in PRP at 4 days (when lung injury first appears), 7 days (when pulmonary arterial pressure first increases), and 14 days after treatment with MCTP (when RVE is evident). At 4, 7, or 14 days following treatment there was no difference in the concentration of TxB2 in unstimulated PRP from MCTP-treated and control rats. Following stimulation with arachidonic acid, the release of TxB2 at maximal aggregation was not different in PRP from MCTP-treated and control rats at any time after treatment. The rate of release of TxB2 was lower in PRP from rats treated with MCTP 7 days earlier, but was not different at any other time following treatment. At concentrations up to 250 micrograms/ml, MCTP added in vitro to PRP from untreated rats did not affect the concentration of TxB2 released during aggregation induced by arachidonic acid. Only at very high concentrations (1 mg/ml) did MCTP abolish the aggregation response and depress TxB2 release in PRP. These results indicate that MCTP treatment does not affect platelet 5HT content and does not affect basal TxB2 production or TxB2 release by platelets stimulated in vitro.
单猪屎豆碱吡咯（MCTP）是植物毒素单猪屎豆碱的一种代谢产物，其通过未知机制在大鼠中引发肺血管损伤、肺动脉高压和右心室扩大（RVE）。血小板的作用已通过观察得到提示，即抗体诱导的血小板减少可减轻MCTP所致的右心室扩大。血小板可释放多种血管收缩剂，如5-羟色胺（5HT）和血栓素A2（TxA2），这些可能导致肺动脉高压。确定MCTP治疗是否会改变血小板5HT含量或改变富含血小板血浆（PRP）中TxA2对聚集的释放情况很有意义。在MCTP治疗14天后，此时肺动脉高压已确立且出现右心室扩大，处理组和对照组大鼠的洗涤血小板或血小板贫乏血浆中的5HT浓度并无差异。在MCTP治疗1天后，在肺损伤明显之前，处理组大鼠未刺激的PRP中TxA2的稳定代谢产物TxB2的浓度高于对照组大鼠。还在MCTP治疗后4天（肺损伤首次出现时）、7天（肺动脉压首次升高时）和14天（右心室扩大明显时）检测了PRP中的TxB2浓度。在治疗后4、7或14天，MCTP处理组和对照组大鼠未刺激的PRP中TxB2的浓度没有差异。用花生四烯酸刺激后，在治疗后的任何时间，MCTP处理组和对照组大鼠的PRP中最大聚集时TxB2的释放没有差异。7天前用MCTP处理的大鼠的PRP中TxB2的释放速率较低，但在治疗后的任何其他时间没有差异。在体外向未处理大鼠的PRP中添加浓度高达250微克/毫升的MCTP，不影响花生四烯酸诱导聚集期间释放的TxB2的浓度。仅在非常高的浓度（1毫克/毫升）下，MCTP才会消除聚集反应并抑制PRP中TxB2的释放。这些结果表明，MCTP治疗不影响血小板5HT含量，也不影响基础TxB2的产生或体外刺激的血小板释放TxB2。
