5-羟色胺诱导大鼠颈上神经节超极化的药理学特性
Pharmacological characterization of 5-hydroxytryptamine-induced hyperpolarization of the rat superior cervical ganglion.
作者信息
Ireland S J, Jordan C C
机构信息
Department of Neuropharmacology, Glaxo Group Research Ltd., Ware, Hertfordshire.
出版信息
Br J Pharmacol. 1987 Oct;92(2):417-27. doi: 10.1111/j.1476-5381.1987.tb11338.x.
1 A study has been made of the pharmacology of 5-hydroxytryptamine (5-HT)-induced hyperpolarization responses recorded extracellularly from the rat isolated superior cervical ganglion (SCG). 2 Hyperpolarization responses induced by 5-HT (1 X 10(-8)-1 X 10(-4) M) in the presence of MDL 72222 (1 X 10(-5) M) were not antagonized by phentolamine (1 X 10(-6) M), prazosin (1 X 10(-7)-3 X 10(-7) M), haloperidol (1 X 10(-6) M) or ketanserin (1 X 10(-7)-1 X 10(-6) M). However, the latter two compounds both potentiated and increased the persistence of the hyperpolarization induced by moderate to high concentrations of 5-HT. Spiperone (1 X 10(-7) M) caused similar effects. All further experiments were performed in the presence of ketanserin (1 X 10(-6) M) as well as MDL 72222. 3 8-Hydroxy-2(di-n-propylamino)-tetralin (8-OH-DPAT; 1 X 10(-7)-1 X 10(-4) M) and ipsapirone (3 X 10(-5)-3 X 10(-4) M) behaved as weak hyperpolarizing agonists on the SCG. However, at concentrations below those required to produce hyperpolarization, both compounds acted as unsurmountable antagonists of 5-HT-induced hyperpolarization. 4 5-Carboxamidotryptamine (5-CT; 1 X 10(-9)-1 X 10(-5) M) mimicked the hyperpolarizing activity of 5-HT on the SCG. The EC50 for 5-CT was approximately 9 fold lower than that for 5-HT. 5 Spiperone (1 X 10(-7) - 1 X 10(-5) M) behaved as a reversible competitive antagonist of hyperpolarization responses induced by 5-HT with a pKB value of 7.40 +/- 0.09. Spiperone (1 X 10(-7)-1 X 10(-6) M) also caused concentration-dependent rightward displacement of the 5-CT concentration-hyperpolarization response curve. In this case, the pKB was 7.80 +/- 0.05. 6 (+/-)-Cyanopindolol (3 X 10(-7)-3 X 10(-6) M) caused non-parallel rightward displacements of the 5-HT concentration-response curve. Against 5-CT, (+/-)-cyanopindolol (3 X 10(-7)-3 X 10(-6) M) caused a concentration-independent rightward displacement of the concentration-response curve, accompanied by a large increase in the maximum response. 5-CT-induced hyperpolarization recorded in the presence of (+/-)-cyanopindolol (3 X 10(-7) M) was not significantly antagonized by methiothepin (1 X 10(-6) M) or methysergide (1 X 10(-6) M). 7. It is concluded that 5-HT-induced hyperpolarization of the rat SCG is mediated via a 5-HT1-like receptor which resembles the 5-HT1A binding site. However, a lack of selective drugs precludes more definitive characterization of this receptor.
对从大鼠离体颈上神经节（SCG）细胞外记录的5-羟色胺（5-HT）诱导的超极化反应进行了药理学研究。
在MDL 72222（1×10⁻⁵ M）存在的情况下，5-HT（1×10⁻⁸ - 1×10⁻⁴ M）诱导的超极化反应不受酚妥拉明（1×10⁻⁶ M）、哌唑嗪（1×10⁻⁷ - 3×10⁻⁷ M）、氟哌啶醇（1×10⁻⁶ M）或酮色林（1×10⁻⁷ - 1×10⁻⁶ M）的拮抗。然而，后两种化合物既增强了中等至高浓度5-HT诱导的超极化，又增加了其持续性。螺哌隆（1×10⁻⁷ M）产生了类似的效果。所有进一步的实验均在酮色林（1×10⁻⁶ M）以及MDL 72222存在的情况下进行。
8-羟基-2（二正丙基氨基）四氢萘（8-OH-DPAT；1×10⁻⁷ - 1×10⁻⁴ M）和ipsapirone（3×10⁻⁵ - 3×10⁻⁴ M）在SCG上表现为弱超极化激动剂。然而，在产生超极化所需浓度以下，这两种化合物均作为5-HT诱导超极化的不可逾越拮抗剂起作用。
5-羧酰胺基色胺（5-CT；1×10⁻⁹ - 1×10⁻⁵ M）模拟了5-HT对SCG的超极化活性。5-CT的EC50比5-HT的约低9倍。
螺哌隆（1×10⁻⁷ - 1×10⁻⁵ M）作为5-HT诱导的超极化反应的可逆竞争性拮抗剂，pKB值为7.40±0.09。螺哌隆（1×10⁻⁷ - 1×10⁻⁶ M）也使5-CT浓度-超极化反应曲线产生浓度依赖性的右移。在这种情况下，pKB为7.80±0.05。
（±）-氰吲哚洛尔（3×10⁻⁷ - 3×10⁻⁶ M）使5-HT浓度-反应曲线发生非平行右移。对于5-CT，（±）-氰吲哚洛尔（3×10⁻⁷ - 3×10⁻⁶ M）使浓度-反应曲线发生与浓度无关的右移，同时最大反应大幅增加。在（±）-氰吲哚洛尔（3×10⁻⁷ M）存在下记录的5-CT诱导的超极化不受甲硫噻平（1×10⁻⁶ M）或甲基麦角新碱（1×10⁻⁶ M）的显著拮抗。
得出结论：5-HT诱导的大鼠SCG超极化是通过类似于5-HT1A结合位点的5-HT1样受体介导的。然而，缺乏选择性药物妨碍了对该受体更确切的表征。
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