Challet E, Naylor E, Metzger J M, MacIntyre D E, Turek F W
Center for Circadian Biology and Medicine, Department of Neurobiology and Physiology, Northwestern University, 2153 North Campus Drive, Evanston, IL 60208, USA.
Brain Res. 1998 Jul 27;800(1):32-9. doi: 10.1016/s0006-8993(98)00491-0.
Substance P (SP) is a neuromodulator which may participate in the photic regulation of the circadian timing system in mammals. The biological effects of SP are mediated by interaction with specific receptors, designated as NK1, NK2, and NK3. The NK1 subtype receptor is expressed in the circadian system. Experiment 1 was designed to test whether an NK1 antagonist mimics the effects of dark pulses. Hamsters were housed in constant lighting conditions, either constant darkness or constant light (around 250 lx), and they received an i.p. injection of either the specific NK1 receptor antagonist, L-760,735 (5 mg/kg), or saline during the mid-subjective day, a time when dark pulses cause a phase-advance in circadian rhythm of locomotor activity. After treatment with the NK1 antagonist, significant phase-advances of wheel-running activity rhythm were found in constant light, but not in constant darkness. Experiment 2 was designed to test the ability of the NK1 antagonist to block the phase-delaying and/or the phase-advancing effects of light in animals kept in constant darkness. Phase-advances of locomotor activity rhythm that can normally be induced by light pulses given during the late subjective night were markedly reduced by pre-treatment with the NK1 antagonist. By contrast, phase-delays that can be induced by lights pulses given during the early subjective night were unaffected by the NK1 antagonist. These data support the hypothesis that SP within the circadian system may, by interacting with NK1 receptors, modulate photic responses of the SCN pacemaker.
P物质（SP）是一种神经调质，可能参与哺乳动物昼夜节律系统的光调节。SP的生物学效应是通过与特定受体（称为NK1、NK2和NK3）相互作用介导的。NK1亚型受体在昼夜节律系统中表达。实验1旨在测试NK1拮抗剂是否模拟暗脉冲的作用。将仓鼠饲养在恒定光照条件下，即持续黑暗或恒定光照（约250勒克斯），在主观日中午，即暗脉冲会导致运动活动昼夜节律提前的时间，给它们腹腔注射特定的NK1受体拮抗剂L-760,735（5毫克/千克）或生理盐水。用NK1拮抗剂处理后，在恒定光照条件下发现轮转活动节律有显著的提前，但在持续黑暗条件下没有。实验2旨在测试NK1拮抗剂阻断在持续黑暗中饲养的动物中光的相位延迟和/或相位提前效应的能力。在主观夜后期给予光脉冲通常可诱导的运动活动节律的相位提前，经NK1拮抗剂预处理后明显降低。相比之下，在主观夜早期给予光脉冲可诱导的相位延迟不受NK1拮抗剂影响。这些数据支持这样的假设，即昼夜节律系统中的SP可能通过与NK1受体相互作用，调节视交叉上核起搏器的光反应。
