POTENTIAL ANTICONVULSIVE PROPERTIES OF ENDOGENOUS PROSTAGLANDINS FORMED IN MOUSE-BRAIN
POTENTIAL ANTICONVULSIVE PROPERTIES OF ENDOGENOUS PROSTAGLANDINS FORMED IN MOUSE-BRAIN
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DOI：
10.1016/0006-8993(82)90225-6
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发表时间：
1982-01-01
期刊：
影响因子：
2.9
通讯作者：
HERTTING, G
中科院分区：
文献类型：
--
作者：
FORSTERMANN, U;HELDT, R;HERTTING, G
采用特异性放射免疫法测定小鼠全脑体内形成的5种不同前列腺素类化合物（PGD2、PGF2α、PGE2、TXB2和6-keto-PGF1α）的水平。发现基础浓度非常低（几纳克/克湿重）。在戊四唑或电惊厥休克引起的惊厥期间发生显着增加。在这两种情况下，检测到的主要环氧合酶产物是 PGD2，其次是 PGF2α 和较低浓度的其他前列腺素。非甾体类抗炎药氟比洛芬、吲哚美辛和双氯芬酸剂量依赖性地抑制戊四唑诱导的前列腺素形成。同时，这3种化合物剂量依赖性地增加戊四唑的急性毒性（LD50降低）。相反，如果通过先前的电击提高脑前列腺素水平，则戊四唑的毒性显着降低（LD50增加），并且阵挛发作的发作时间显着延长。如果吲哚美辛阻止大脑前列腺素合成，或者延长电击与戊四唑给药之间的时间间隔，使电击刺激的前列腺素浓度再次降至基础水平，则对潜伏期和LD50的影响都可以逆转。这些发现表明，惊厥期间小鼠大脑中形成的内源性前列腺素可能具有抗惊厥特性。
The levels of 5 different prostanoids (PGD2, PGF2α, PGE2, TXB2and 6-keto-PGF1α) formed in whole mouse brain in vivo were measured by specific radioimmunoassays. Basal concentrations were found to be very low (few ng/g wet weight). A marked increase occurred during convulsions induced by either pentylenetetrazole or by electroconvulsive shock. Under both conditions the major cyclooxygenase product detected was PGD2, followed by PGF2α and lower concentrations of the other prostanoids.The non-steroidal anti-inflammatory drugs flurbiprofen, indomethacin, and diclofenac dose-dependently inhibited the pentylenetetrazole-induced formation of prostaglandins. Concomitantly these 3 compounds dose-dependently increased the acute toxicity of pentylenetetrazole (decrease in LD50).Conversely, if levels of cerebral prostaglandins were enhanced by a preceding electroshock, the toxicity of pentylenetetrazole was significantly reduced (increase in LD50), and the time of onset of clonic seizures was markedly prolonged. Both the effect on the latency time and the LD50could be reversed if the cerebral prostaglandin synthesis was prevented by indomethacin, or if the time interval between the electroshock and pentylenetetrazole administration was extended, so that the electroshock-stimulated prostaglandin concentrations had declined to basal levels again. These findings indicate that endogenous prostanoids formed in mouse brain during convulsions might possess anticonvulsive properties.