Role of prostaglandins in spinal transmission of the exercise pressor reflex in decerebrated rats.
Role of prostaglandins in spinal transmission of the exercise pressor reflex in decerebrated rats.
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前列腺素在去大脑大鼠运动升压反射脊髓传递中的作用。
DOI：
10.1016/j.neuroscience.2014.06.061
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发表时间：
2014
期刊：
影响因子：
3.3
通讯作者：
Kaufman,MP
中科院分区：
文献类型：
--
作者：
Stone,AJ;Copp,SW;Kaufman,MP
先前的研究发现，骨骼肌中的前列腺素在诱发运动升压反射方面发挥着作用；然而，前列腺素在反射的脊髓传递中所起的作用尚不清楚。因此，我们确定了脊髓阻滞环氧合酶（COX）活性和/或脊髓阻滞内过氧化物（EP）2或4受体是否会减弱去大脑大鼠的运动升压反射。我们首先确定了非特异性COX抑制剂酮咯酸（10μg，10μl）、COX-2特异性抑制剂塞来考昔（100μg，10μl）、EP2拮抗剂PF-04418948（10μg，10μl）和EP4拮抗剂L-161,982（4μg，每μl）的鞘内剂量。 10 µl）分别有效减弱鞘内注射花生四烯酸（10 µl 中 100 µg）、EP2 激动剂布他前列素（10 µl 中 4 ng）和 EP4 激动剂 TCS 2510（2.5 µl 中 6.25 µg）的升压反应。一旦确定了有效剂量，我们在鞘内注射酮咯酸、塞来考昔、EP2拮抗剂和EP4拮抗剂之前和之后静态收缩后肢。我们发现酮咯酸显着减弱了对静态收缩的升压反应（酮咯酸之前：23 ± 5 mmHg，酮咯酸之后 14 ± 5 mmHg；p < 0.05），而塞来昔布则没有效果。我们还发现，8 µg L-161,982（而非 4 µg L-161,982）显着减弱了对静态收缩的升压反应（L-161,982 之前：21 ± 4 mmHg，L-161,982 之后 12 ± 3 mmHg；p< 0.05），而PF-04418948 (10 µg) 没有效果。我们得出的结论是，脊髓COX-1（而不是COX-2）在诱发运动升压反射方面发挥作用，并且由这种酶产生的脊髓前列腺素很可能激活脊髓EP4受体，而不是EP2受体。
Previous studies found that prostaglandins in skeletal muscle play a role in evoking the exercise pressor reflex; however the role played by prostaglandins in the spinal transmission of the reflex is not known. We determined, therefore, whether or not spinal blockade of cyclooxygenase (COX) activity and/or spinal blockade of endoperoxide (EP) 2 or 4 receptors attenuated the exercise pressor reflex in decerebrated rats. We first established that intrathecal doses of a non-specific COX inhibitor Ketorolac (100 μg in 10 μl), a COX-2-specific inhibitor Celecoxib (100 μg in 10 μl), an EP2 antagonist PF-04418948 (10 μg in 10 μl), and an EP4 antagonist L-161,982 (4 μg in 10 μl) effectively attenuated the pressor responses to intrathecal injections of arachidonic acid (100 μg in 10 μl), EP2 agonist Butaprost (4 ng in 10 μl), and EP4 agonist TCS 2510 (6.25 μg in 2.5 μl), respectively. Once effective doses were established, we statically contracted the hind limb before and after intrathecal injections of Ketorolac, Celecoxib, the EP2 antagonist and the EP4 antagonist. We found that Ketorolac significantly attenuated the pressor response to static contraction (before Ketorolac: 23 ± 5 mmHg, after Ketorolac 14 ± 5 mmHg;p< 0.05) whereas Celecoxib had no effect. We also found that 8 μg of L-161,982, but not 4 μg of L-161,982, significantly attenuated the pressor response to static contraction (before L-161,982: 21 ± 4 mmHg, after L-161,982 12 ± 3 mmHg;p< 0.05), whereas PF-04418948 (10 μg) had no effect. We conclude that spinal COX-1, but not COX-2, plays a role in evoking the exercise pressor reflex, and that the spinal prostaglandins produced by this enzyme are most likely activating spinal EP4 receptors, but not EP2 receptors.