Lepre M, Olpe H R, Evans R H, Brugger F
Research and Development Department, Ciba-Geigy Ltd., Basel, Switzerland.
Eur J Pharmacol. 1994 Jun 2;258(1-2):23-31. doi: 10.1016/0014-2999(94)90053-1.
The goal of these investigations was to study the role of tachykinin NK2 receptors in neonatal spinal cords using the selective NK2 receptor agonist [beta-Ala8]neurokinin A-(4-10) and the new NK2 receptor antagonist GR 94800. Experiments were performed with superfused hemisected rat and gerbil spinal cords. Dorsal roots were electrically stimulated and the synaptically elicited responses and the DC-potentials were recorded extracellularly from the corresponding ventral roots. [beta-Ala8]neurokinin A-(4-10) depolarized ventral roots (0.01-10 microM) and increased their spontaneous activity in a concentration-dependent manner. These effects of [beta-Ala8]neurokinin A-(4-10) were reduced by GR 94800. The action of GR 94800 was selective because the depolarizing effects of similar magnitude evoked by the NK1 receptor agonist [Sar9,Met(O2)11]substance P were not affected by GR 94800. The pA2 values of GR 94800 amounted to 6.0 +/- 0.4 in the rat and 5.4 +/- 0.3 in the gerbil. The NK2 receptor agonist was more potent in the rat than in the gerbil. The estimated EC50 (mean +/- S.E.M.) was found to be 3.9 + 6.0/-1.3 microM in the rat and 2.4 + 2.9/-1.3 microM in the gerbil spinal cord. The NK2 receptor agonist [beta-Ala8]neurokinin A-(4-10) potentiated the monosynaptic reflex evoked by dorsal root stimulation. The potentiation manifested itself as an increase in the amplitude of the early component of the response. The receptor type mediating this effect could not be elucidated. The potentiation ranged between 30 +/- 27 and 110 +/- 36% (0.3 and 10 microM), respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
这些研究的目的是使用选择性NK2受体激动剂[β-丙氨酸8]神经激肽A-(4-10)和新型NK2受体拮抗剂GR 94800，研究速激肽NK2受体在新生脊髓中的作用。实验采用了灌流的大鼠和沙鼠半切脊髓标本。对背根进行电刺激，并从相应的腹根细胞外记录突触诱发反应和直流电位。[β-丙氨酸8]神经激肽A-(4-10)使腹根去极化(0.01-10微摩尔)，并以浓度依赖的方式增加其自发活动。GR 94800可减弱[β-丙氨酸8]神经激肽A-(4-10)的这些作用。GR 94800的作用具有选择性，因为NK1受体激动剂[Sar9,Met(O2)11]P物质诱发的类似幅度的去极化作用不受GR 94800影响。GR 94800在大鼠中的pA2值为6.0±0.4，在沙鼠中为5.4±0.3。NK2受体激动剂在大鼠中的效力高于沙鼠。估计的EC50(平均值±标准误)在大鼠脊髓中为3.9+6.0/-1.3微摩尔，在沙鼠脊髓中为2.4+2.9/-1.3微摩尔。NK2受体激动剂[β-丙氨酸8]神经激肽A-(4-10)增强了背根刺激诱发的单突触反射。这种增强表现为反应早期成分幅度的增加。介导这种效应的受体类型尚不清楚。增强幅度分别在30±27%至110±36%(0.3和10微摩尔)之间。(摘要截短于250字)
