Seabrook G R, Bowery B J, Hill R G
Department of Pharmacology, Merck Sharp and Dohme Research Laboratories, Terlings Park, Harlow, Essex, UK.
Eur J Pharmacol. 1995 Jan 24;273(1-2):113-9. doi: 10.1016/0014-2999(94)00681-v.
The pharmacology of tachykinin receptors within the ventral tegmental area of rat brain slices was studied using in vitro electrophysiological techniques. The selective tachykinin NK3 receptor agonist senktide (100 nM) increased the action potential firing rate from 1.9 to 3.9 Hz in 70% of spontaneously active cells tested (n = 27). Senktide was the most potent agonist tested with an EC50 of 4 nM. In contrast the NK1 receptor agonists substance P-O-methyl ester (100-300 nM) or GR 73632 (1 microM) were inactive at the concentrations tested. Responses to neurokinin B (EC50 = 32 nM) were not blocked by the tachykinin NK1 receptor antagonist CP 99,994 (1 microM) nor by the tachykinin NK2 receptor antagonist SR 48968 (300 nM). Similarly responses to the tachykinin NK2 receptor agonist beta-[Ala8]neurokinin A-(4-10) (EC50 = 427 nM) were not antagonised by the tachykinin NK2 receptor antagonist SR 48968 (300 nM) and thus were likely to be due to the activation of tachykinin NK3 receptors. These data demonstrate that NK3, and not NK1 or NK2 receptors, mediate the principal excitatory effects of exogenously applied tachykinin receptor agonists on dopamine neurones within the rat ventral tegmental area.
利用体外电生理技术研究了大鼠脑片腹侧被盖区内速激肽受体的药理学特性。选择性速激肽NK3受体激动剂senktide（100 nM）使70%的受试自发活动细胞（n = 27）的动作电位发放频率从1.9 Hz增加到3.9 Hz。Senktide是所测试的最有效的激动剂，其EC50为4 nM。相比之下，NK1受体激动剂P物质-O-甲酯（100 - 300 nM）或GR 73632（1 μM）在所测试的浓度下无活性。对神经激肽B（EC50 = 32 nM）的反应未被速激肽NK1受体拮抗剂CP 99,994（1 μM）或速激肽NK2受体拮抗剂SR 48968（300 nM）阻断。同样，对速激肽NK2受体激动剂β-[Ala8]神经激肽A-(4 - 10)（EC50 = 427 nM）的反应未被速激肽NK2受体拮抗剂SR 48968（300 nM）拮抗，因此可能是由于速激肽NK3受体的激活所致。这些数据表明，介导外源性应用的速激肽受体激动剂对大鼠腹侧被盖区内多巴胺神经元主要兴奋作用的是NK3受体，而非NK1或NK2受体。
