Starkey S J, Skingle M
Department of Pharmacology, Glaxo Research and Development Ltd., Ware, Herts, U.K.
Neuropharmacology. 1994 Mar-Apr;33(3-4):393-402. doi: 10.1016/0028-3908(94)90069-8.
5-Hydroxytryptamine (5-HT) release was measured by fast cyclic voltammetry in guinea-pig dorsal raphé nucleus slices. Release was reproducibly evoked by a single 0.1 msec pulse of electrical stimulation. The 5-HT1A receptor agonist 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH DPAT) produced a concentration-related inhibition of the stimulated 5-HT release, with 50% inhibition at 47 nM. This inhibition was competitively antagonized by N-tert-butyl 3-4-(2-methoxypheny)piperazin-1-yl-2- phenylpropanamide dihydrochloride [(+/-)WAY 100135], a selective 5-HT1A receptor antagonist (pA2 = 7.9). The 5-HT1D receptor agonist sumatriptan also produced a concentration-related inhibition of 5-HT release, with 50% inhibition at 40 nM. The effect of sumatriptan on 5-HT release was antagonized by the 5-HT1D receptor antagonist 2'-methyl-4'-(5-methyl-[1,2,4]oxadiazol-3-yl)-biphenyl-4-carboxyli c acid [4-methoxy-3-(4-methyl-piperazin-1-yl)-phenyl]-amide (GR127935) (pA2 = 8.7). Both (+/-)WAY 100135 and GR127935 increased the 5-HT release evoked by a train of 5 pulses at 1 Hz, suggesting that they were antagonizing the feedback of endogenously released 5-HT onto its autoreceptors. These findings demonstrate for the first time the presence of functional 5-HT1D as well as 5-HT1A autoreceptors in the guinea-pig dorsal raphé nucleus.
采用快速循环伏安法在豚鼠中缝背核切片中测定5-羟色胺（5-HT）的释放。单次0.1毫秒的电刺激脉冲可重复性地诱发释放。5-HT1A受体激动剂8-羟基-2-（二正丙基氨基）四氢萘（8-OH DPAT）对刺激引起的5-HT释放产生浓度依赖性抑制，在47 nM时抑制率达50%。这种抑制作用被选择性5-HT1A受体拮抗剂N-叔丁基-3- [4-（2-甲氧基苯基）哌嗪-1-基]-2-苯基丙酰胺二盐酸盐[（±）WAY 100135]竞争性拮抗（pA2 = 7.9）。5-HT1D受体激动剂舒马曲坦也对5-HT释放产生浓度依赖性抑制，在40 nM时抑制率达50%。舒马曲坦对5-HT释放的作用被5-HT1D受体拮抗剂2'-甲基-4'-（5-甲基-[1,2,4]恶二唑-3-基）-联苯-4-羧酸[4-甲氧基-3-（4-甲基-哌嗪-1-基）-苯基]-酰胺（GR127935）拮抗（pA2 = 8.7）。（±）WAY 100135和GR127935均增加了1 Hz下5个脉冲串诱发的5-HT释放，表明它们正在拮抗内源性释放的5-HT对其自身受体的反馈作用。这些发现首次证明了豚鼠中缝背核中存在功能性5-HT1D以及5-HT1A自身受体。
