Surprenant A, North R A, Katayama Y
Neuroscience. 1987 Jan;20(1):189-99. doi: 10.1016/0306-4522(87)90011-x.
Intracellular recordings were made from neurons of the guinea pig submucosal plexus and the effects of substance P and the substance P analogue [D-Arg1,D-Pro2,D-Trp7,9,Leu11]substance P were examined. Substance P (20-200 nM) depolarized all submucosal neurons; these depolarizations were shown to be due to a decrease in the resting (or "leak") potassium conductance of the membrane. In approximately 50% of the 46 neurons tested, superfusion with [D-Arg1,D-Pro2,D-Trp7,9,Leu11]substance P (0.2-20 microM) produced a dose-dependent membrane hyperpolarization. This hyperpolarization was prevented by the alpha 2-adrenoceptor antagonist idazoxan (300 nM) or by concentrations of cobalt which abolished all spontaneous and evoked synaptic potentials, indicating that it resulted from release of noradrenaline from sympathetic nerve terminals. [D-Arg1,D-Pro2,D-Trp7,9,Leu11]substance P depressed the amplitude of the three synaptic potentials recorded from submucosal neurons; the concentrations that caused 50% of the maximal inhibition of the fast excitatory postsynaptic potential, the inhibitory postsynaptic potential, and slow excitatory postsynaptic potential were 40 microM, 600 nM and 20 microM, respectively. When idazoxan was present, the substance P analogue was less effective in depressing the amplitudes of the fast and slow excitatory synaptic potentials suggesting that much of its presynaptic inhibition also resulted from release of noradrenaline. These results provide evidence that [D-Arg1,D-Pro2,D-Trp7,9,Leu11]substance P releases noradrenaline from sympathetic nerves in the submucosal plexus. One effect of this is a membrane hyperpolarization; another is a presynaptic inhibition of transmitter release. These actions much limit the usefulness of this "substance P antagonist" in efforts to show that synaptic potentials, such as the slow excitatory synaptic potential, are mediated by substance P.
对豚鼠黏膜下神经丛的神经元进行了细胞内记录，并研究了P物质和P物质类似物[D-精氨酸1，D-脯氨酸2，D-色氨酸7,9，亮氨酸11]P物质的作用。P物质（20-200 nM）使所有黏膜下神经元去极化；这些去极化被证明是由于膜的静息（或“泄漏”）钾电导降低所致。在测试的46个神经元中，约50%的神经元用[D-精氨酸1，D-脯氨酸2，D-色氨酸7,9，亮氨酸11]P物质（0.2-20 microM）灌流后产生了剂量依赖性的膜超极化。α2-肾上腺素能拮抗剂咪唑克生（300 nM）或能消除所有自发和诱发突触电位的钴浓度可阻止这种超极化，这表明它是由交感神经末梢释放去甲肾上腺素所致。[D-精氨酸1，D-脯氨酸2，D-色氨酸7,9，亮氨酸11]P物质降低了从黏膜下神经元记录到的三种突触电位的幅度；引起快速兴奋性突触后电位、抑制性突触后电位和慢速兴奋性突触后电位最大抑制的50%的浓度分别为40 microM、600 nM和20 microM。当存在咪唑克生时，P物质类似物在降低快速和慢速兴奋性突触电位幅度方面的效果较差，这表明其大部分突触前抑制也源于去甲肾上腺素的释放。这些结果提供了证据，表明[D-精氨酸1，D-脯氨酸2，D-色氨酸7,9，亮氨酸11]P物质可从黏膜下神经丛的交感神经释放去甲肾上腺素。其作用之一是膜超极化；另一个作用是对递质释放的突触前抑制。这些作用极大地限制了这种“P物质拮抗剂”在试图证明诸如慢速兴奋性突触电位等突触电位由P物质介导的研究中的实用性。
