Galarraga E, Hernández-López S, Tapia D, Reyes A, Bargas J
Departamento de Biofísica, Instituto de Fisiología Celular, UNAM, México City DF, México.
Synapse. 1999 Jul;33(1):26-35. doi: 10.1002/(SICI)1098-2396(199907)33:1<26::AID-SYN3>3.0.CO;2-4.
Substance P (SP) acts as a neurotransmitter in the neostriatum through the axon collaterals of spiny projection neurons. However, possible direct or indirect actions of SP on the neostriatal output neurons have not been described. Targets of SP terminals within the neostriatum include interneurons, spiny neurons, afferent fibers and boutons. SP induces the release of both dopamine (DA) and acetylcholine (ACh). Since some postsynaptic actions of both DA and ACh on spiny neurons are known, we asked if activation of neostriatal NK1-class receptors is able to reproduce them. The SP NK1-receptor agonist, GR73632 (1 microM), had both excitatory and inhibitory actions on virtually all spiny neurons tested at resting potential. The excitatory action was blocked by atropine and coursed with an increase in firing rate and input resistance (R(N)). The inhibitory action was blocked by haloperidol and coursed with a reduction in firing rate and R(N). Therefore, the release of both DA and ACh induced by NK1-receptor activation modulates indirectly the excitability of the projection neurons. SP facilitates the actions of these transmitters on the spiny neuron. A residual excitatory response to the NK1-receptor agonist was observed in 30% of a sample of neurons tested in the presence of both haloperidol and atropine. The increase in R(N) that accompanied this response could be observed in the presence of 1 microM TTX or 100 microM Cd2+, suggesting a direct effect. Double labeling showed that only SP-immunoreactive neurons were facilitated by NK1-receptor activation in these conditions.
P物质（SP）通过棘状投射神经元的轴突侧支在新纹状体中充当神经递质。然而，SP对新纹状体输出神经元可能的直接或间接作用尚未见描述。新纹状体内SP终末的靶点包括中间神经元、棘状神经元、传入纤维和终扣。SP可诱导多巴胺（DA）和乙酰胆碱（ACh）的释放。由于已知DA和ACh对棘状神经元的一些突触后作用，我们探究新纹状体NK1类受体的激活是否能够重现这些作用。SP NK1受体激动剂GR73632（1微摩尔）对几乎所有在静息电位下测试的棘状神经元均有兴奋和抑制作用。兴奋作用被阿托品阻断，且伴随着放电频率和输入电阻（R(N)）的增加。抑制作用被氟哌啶醇阻断，且伴随着放电频率和R(N)的降低。因此，NK1受体激活诱导的DA和ACh释放间接调节投射神经元的兴奋性。SP促进这些递质对棘状神经元的作用。在同时存在氟哌啶醇和阿托品的情况下，在30%的测试神经元样本中观察到对NK1受体激动剂的残余兴奋反应。在存在1微摩尔TTX或100微摩尔Cd2+的情况下，可观察到伴随该反应的R(N)增加，提示存在直接作用。双重标记显示，在这些条件下，只有SP免疫反应性神经元被NK1受体激活所促进。
