Armstead W M
Department of Anesthesia, University of Pennsylvania, Children's Hospital of Philadelphia 19104, USA.
Am J Physiol. 1996 Jul;271(1 Pt 2):H166-72. doi: 10.1152/ajpheart.1996.271.1.H166.
It has been observed that prostaglandins (PG) PGE2 and PGI2 increased cortical periarachnoid cerebrospinal fluid (CSF) methionine enkephalin (Met-enk) and leucine enkephalin (Leu-enk) concentrations in the newborn pig. It was also observed that PG-induced pial artery dilation was associated with elevated CSF guanosine 3',5'-cyclic monophosphate (cGMP) and adenosine 3',5'-cyclic monophosphate (cAMP) levels in the piglet. However, other studies have not always supported a role for cGMP in PG dilation. The present study used a pharmacological approach to test the hypothesis that both cGMP and cAMP contribute to PG-induced pial dilation and associated elevated CSF opioid concentration. PGE2 produced pial vasodilation that was blunted by the Rp diastereomer of bromoguanosine 3',5'-cyclic monophosphothioate [Rp-8-BrcGMPS (10(-5)M)], a cGMP antagonist (9 +/- 1, 16 +/- 1, and 23 +/- 1 vs. 4 +/- 1, 6 +/- 1, and 9 +/- 1% for 1, 10, and 100 ng/ml PGE2 before and after Rp-8-BrcGMPS, respectively). PGE2 elevated CSF Met-enk concentration, and these biochemical changes were also blunted by Rp-8-BrcGMPS (1,001 +/- 23, 1,424 +/- 54, and 1,973 +/- 56 vs. 804 +/- 41, 988 +/- 52, and 1,222 +/- 21 pg/ml for control, 10, and 100 ng/ml PGE2 in the absence and presence of Rp-8-BrcGMPS, respectively). Similar biochemical and vascular effects of Rp-8-BrcGMPS were observed for PGI2. Additionally, the Rp diastereomer of bromoadenosine 3',5'-cyclic monophosphothioate [Rp-8-BrcAMPS (10(-5)M)], a cAMP antagonist, blunted PGE2 dilation (10 +/- 1, 15 +/- 1, and 24 +/- 1 vs. 5 +/- 1, 8 +/- 1, and 12 +/- 1% for 1, 10, and 100 ng/ml PGE2 before and after Rp-8-BrcAMPS, respectively). PGE2-associated increases in CSF Met-enk and Leu-enk were similarly blunted by Rp-8-BrcAMPS. These data show that both cGMP and cAMP contribute to PG-induced pial dilation and that PG-associated elevated CSF cGMP and cAMP levels result in increased CSF Met-enk and Leu-enk concentration.
据观察，前列腺素（PG）PGE2和PGI2可增加新生猪大脑皮质蛛网膜下腔脑脊液（CSF）中甲硫氨酸脑啡肽（Met-enk）和亮氨酸脑啡肽（Leu-enk）的浓度。还观察到，PG诱导的软脑膜动脉扩张与仔猪脑脊液中鸟苷3',5'-环磷酸（cGMP）和腺苷3',5'-环磷酸（cAMP）水平升高有关。然而，其他研究并不总是支持cGMP在PG扩张中起作用。本研究采用药理学方法来检验cGMP和cAMP均有助于PG诱导的软脑膜扩张以及相关脑脊液阿片类物质浓度升高这一假设。PGE2可引起软脑膜血管舒张，而cGMP拮抗剂3',5'-环磷酸鸟苷溴代硫代磷酸酯的Rp非对映体[Rp-8-BrcGMPS（10(-5)M）]可减弱这种舒张作用（对于1、10和100 ng/ml PGE2，在给予Rp-8-BrcGMPS前后，分别为9±1、16±1和23±1对4±1、6±1和9±1%）。PGE2可提高脑脊液Met-enk浓度，这些生化变化也可被Rp-8-BrcGMPS减弱（对于对照、10和100 ng/ml PGE2，在不存在和存在Rp-8-BrcGMPS的情况下，分别为1001±23、1424±54和1973±56对804±41、988±52和1222±21 pg/ml）。对于PGI2，观察到Rp-8-BrcGMPS具有类似的生化和血管效应。此外，cAMP拮抗剂3',5'-环磷酸腺苷溴代硫代磷酸酯的Rp非对映体[Rp-8-BrcAMPS（10(-5)M）]可减弱PGE2的扩张作用（对于1、10和100 ng/ml PGE2，在给予Rp-8-BrcAMPS前后，分别为10±1、15±1和24±1对5±1、8±1和12±1%）。PGE2相关的脑脊液Met-enk和Leu-enk增加也同样被Rp-8-BrcAMPS减弱。这些数据表明，cGMP和cAMP均有助于PG诱导的软脑膜扩张，并且PG相关的脑脊液cGMP和cAMP水平升高导致脑脊液Met-enk和Leu-enk浓度增加。
