Vass Z, Nuttall A L, Coleman J K, Miller J M
Kresge Hearing Research Institute, Department of Otolaryngology, University of Michigan, Ann Arbor 48109-0506.
Hear Res. 1995 Sep;89(1-2):86-92. doi: 10.1016/0378-5955(95)00127-4.
Physiological evidence from several studies suggests that endogenous vasoactive peptides, such as substance P (SP), and their respective receptor populations may participate in the mechanisms that govern the autoregulatory capacity of the cochlear vascular system. However, these studies do not provide evidence regarding the origin or mechanism of action of SP. Capsaicin sensitivity has been used as a marker for sensory neurons, and the release of SP following capsaicin treatment suggests a sensory transmitter role for SP. The present investigation examines the relationship between the capsaicin-sensitive sensory neurons and SP in the regulation of cochlear blood flow (CBF). In 75 pigmented guinea pigs, the cochlea was surgically exposed and a laser Doppler flowmeter probe placed on the bony surface of the first turn to monitor CBF. Capsaicin solutions (2 microliters, 0.01%, 0.001% and 0.0001%) applied to the round-window membrane (RWM) resulted in a dose-related CBF increase, without change in the systemic blood pressure. This effect could be inhibited by application of a specific SP receptor antagonist, [D-Pro2,D-Trp7,9]-SP, after which none of the capsaicin concentrations used induced a change in CBF. Moreover, after RWM application of 50 nmol/2 microliters of SP there was a significant increase in CBF. No CBF change was observed with the lower concentrations of 10 nmol SP or 100 pmol SP. These results indicate a role of SP in CBF regulation and give indirect evidence that SP is released from capsaicin-sensitive primary sensory neurons.
多项研究的生理学证据表明,内源性血管活性肽,如P物质(SP)及其各自的受体群体,可能参与了调节耳蜗血管系统自身调节能力的机制。然而,这些研究并未提供关于SP的起源或作用机制的证据。辣椒素敏感性已被用作感觉神经元的标志物,辣椒素处理后SP的释放表明SP具有感觉递质的作用。本研究探讨了辣椒素敏感的感觉神经元与SP在耳蜗血流(CBF)调节中的关系。在75只有色豚鼠中,通过手术暴露耳蜗,并将激光多普勒血流仪探头置于第一圈的骨表面以监测CBF。将辣椒素溶液(2微升,0.01%、0.001%和0.0001%)应用于圆窗膜(RWM)导致CBF呈剂量相关增加,而全身血压无变化。应用特异性SP受体拮抗剂[D-Pro2,D-Trp7,9]-SP可抑制这种效应,此后所用的任何辣椒素浓度均未引起CBF变化。此外,在RWM应用50 nmol/2微升的SP后,CBF显著增加。较低浓度的10 nmol SP或100 pmol SP未观察到CBF变化。这些结果表明SP在CBF调节中起作用,并间接证明SP是从辣椒素敏感的初级感觉神经元释放的。