Namima M, Okamoto K
Jpn J Pharmacol. 1987 Feb;43(2):197-204. doi: 10.1254/jjp.43.197.
The modulatory action of prostaglandin D2 (PGD2) on the high-K+-induced release of 3H-norepinephrine (3H-NE) from rat cerebellar slices was investigated in relation to the presynaptic feedback mechanisms for the NE release. PGD2 (10(-7)-10(5) M) dose-dependently suppressed the release of 3H-NE. The 3H-NE release was also dose-dependently decreased by 10(-10)-5 X 10(-9) M clonidine and increased by 10(-9)-10(-6) M yohimbine, and there was an antagonism between clonidine and yohimbine, indicating the presence of an alpha 2-adrenoceptor-mediated negative feedback mechanism in the rat cerebellum. The inhibitory action of clonidine was not additive to that of PGD2, while there appeared to be an additiveness between the effects of PGD2 and yohimbine. The 3H-NE release was increased by I-isoproterenol and decreased by I-propranolol, but only at concentrations higher than 10(-6) M. PGD2 nearly abolished the actions of these beta-adrenergic agents, and the 3H-NE release remained at a level similar to that induced by 10(-5) M PGD2 alone. Based on these results, it was tentatively suggested that PGD2 inhibits the 3H-NE release by a mechanism independent of adrenoceptor-mediated feedback mechanisms.
研究了前列腺素D2（PGD2）对高钾诱导的大鼠小脑切片中3H-去甲肾上腺素（3H-NE）释放的调节作用，并探讨其与NE释放的突触前反馈机制的关系。PGD2（10^-7 - 10^5 M）剂量依赖性地抑制3H-NE的释放。10^-10 - 5×10^-9 M可乐定也剂量依赖性地降低3H-NE的释放，而10^-9 - 10^-6 M育亨宾则使其增加，并且可乐定与育亨宾之间存在拮抗作用，这表明大鼠小脑中存在α2-肾上腺素能受体介导的负反馈机制。可乐定的抑制作用与PGD2的抑制作用无相加性，而PGD2与育亨宾的作用似乎具有相加性。1-异丙肾上腺素使3H-NE释放增加，1-普萘洛尔使其降低，但仅在浓度高于10^-6 M时出现。PGD2几乎消除了这些β-肾上腺素能药物的作用，3H-NE释放水平与仅由10^-5 M PGD2诱导的水平相似。基于这些结果，初步推测PGD2通过一种独立于肾上腺素能受体介导的反馈机制的机制抑制3H-NE的释放。
