Maggio Nicola, Shavit Efrat, Chapman Joab, Segal Menahem
Department of Neurobiology, The Weizmann Institute, 76100 Rehovot, Israel.
J Neurosci. 2008 Jan 16;28(3):732-6. doi: 10.1523/JNEUROSCI.3665-07.2008.
The effects of thrombin, a blood coagulation serine protease, were studied in rat hippocampal slices, in an attempt to comprehend its devastating effects when released into the brain after stroke and head trauma. Thrombin acting through its receptor, protease-activated receptor 1 (PAR1), produced a long-lasting enhancement of the reactivity of CA1 neurons to afferent stimulation, an effect that saturated the ability of the tissue to undergo tetanus-induced long-term potentiation. This effect was mediated by activation of a PAR1 receptor, because it was shared by a PAR1 agonist, and was blocked by its selective antagonist. An independent effect of thrombin involved the lowering of the threshold for generating epileptic seizures in CA3 region of the hippocampus. Thus, the experiments in a slice mimicked epileptic and cognitive dysfunction induced by thrombin in the brain, and suggest that these effects are mediated by activation of the PAR1 receptor.
凝血酶是一种血液凝固丝氨酸蛋白酶，本研究在大鼠海马切片中对其作用进行了探究，旨在了解其在中风和头部创伤后释放到大脑中时所产生的破坏性影响。凝血酶通过其受体蛋白酶激活受体1（PAR1）发挥作用，使CA1神经元对传入刺激的反应性得到持久增强，这种效应使组织进行破伤风诱导的长时程增强的能力达到饱和。该效应是由PAR1受体的激活介导的，因为PAR1激动剂也具有同样的效应，且被其选择性拮抗剂所阻断。凝血酶的另一个独立作用是降低海马CA3区产生癫痫发作的阈值。因此，切片实验模拟了大脑中凝血酶诱导的癫痫和认知功能障碍，表明这些效应是由PAR1受体的激活介导的。
