Moret C, Briley M
Pierre Fabre Research Center, Castres, France.
Neuropharmacology. 1997 Nov-Dec;36(11-12):1713-23. doi: 10.1016/s0028-3908(97)00145-7.
5-HT autoreceptors involved in the regulation of 5-HT release in the guinea pig dorsal raphe nucleus have been studied in comparison with those in the hypothalamus. In vitro release was measured in slices of raphe and hypothalamus prelabelled with [3H]5-HT, superfused with Krebs solution and depolarized electrically. The non-selective 5-HT receptor agonist, 5-carboxamidotryptamine (5-CT) (0.1-10 nM for raphe: 1-100 nM for hypothalamus) and antagonist, methiothepin (10-1000nM), decreased and increased, respectively, the release of [3H]5-HT evoked by electrical stimulation in either of these regions when given alone. The selective 5-HT1B/D receptor antagonist, GR127935 (100-1000 nM), and the 5-HT1D receptor antagonist, ketanserin (300-1000 nM), had no significant effect on this release in either of these regions. Methiothepin and GR127935 (100-1000 nM) shifted to the right the concentration-effect curve of 5-CT in both the raphe and the hypothalamus. At 300 nM, ketanserin shifted to the right the concentration-effect curve of 5-CT in the raphe but did not modify the 5-CT curve in the hypothalamus. In microdialysis experiments ketanserin, applied locally at 10 microM, increased the extracellular levels of 5-HT in the dorsal raphe nucleus of the freely moving guinea pig, whereas 5-HT levels were unchanged in the hypothalamus. Ketanserin at 1 microM did not affect the decrease in 5-HT output induced by the selective 5-HT1B/D receptor agonist, naratriptan (used at 10 microM in raphe and 0.1 microM in hypothalamus), in the raphe or the hypothalamus. In the raphe, WAY100635, a 5-HT1A receptor antagonist, at 1 microM, did not prevent naratriptan (10 microM) from reducing the extracellular levels of 5-HT. These results suggest that, in the conditions used in this study, the release of 5-HT in the dorsal raphe nucleus is possibly modulated in part by 5-HT1B receptors but essentially the control is through 5-HT receptors whose subtype is still to be determined. In the hypothalamus, however, it is clear that only 5-HT1B receptors are involved in the modulation of 5-HT neurotransmission.
与下丘脑的5-羟色胺（5-HT）自身受体相比，对豚鼠中缝背核中参与5-HT释放调节的自身受体进行了研究。用[3H]5-HT预标记中缝核和下丘脑切片，用Krebs溶液灌流并进行电去极化，测量体外释放。非选择性5-HT受体激动剂5-羧酰胺色胺（5-CT）（中缝核为0.1 - 10 nM，下丘脑为1 - 100 nM）和拮抗剂美噻吨（10 - 1000 nM）单独给药时，分别降低和增加了这两个区域电刺激诱发的[3H]5-HT释放。选择性5-HT1B/D受体拮抗剂GR127935（100 - 1000 nM）和5-HT1D受体拮抗剂酮色林（300 - 1000 nM）对这两个区域的这种释放均无显著影响。美噻吨和GR127935（100 - 1000 nM）使中缝核和下丘脑内5-CT的浓度-效应曲线右移。在300 nM时，酮色林使中缝核内5-CT的浓度-效应曲线右移，但未改变下丘脑内的5-CT曲线。在微透析实验中，局部应用10 μM的酮色林可增加自由活动豚鼠中缝背核细胞外5-HT水平，而下丘脑内5-HT水平未变。1 μM的酮色林不影响选择性5-HT1B/D受体激动剂那拉曲坦（中缝核用10 μM，下丘脑用0.1 μM）在中缝核或下丘脑诱发的5-HT输出减少。在中缝核中，1 μM的5-HT1A受体拮抗剂WAY100635不能阻止那拉曲坦（10 μM）降低细胞外5-HT水平。这些结果表明，在本研究使用的条件下，中缝背核中5-HT的释放可能部分受5-HT1B受体调节，但主要控制是通过其亚型尚待确定的5-HT受体。然而，在下丘脑中，显然只有5-HT1B受体参与5-HT神经传递的调节。
