Chiba Y, Misawa M
Department of Pharmacology, School of Pharmacy, Hoshi University, Tokyo, Japan.
J Appl Physiol (1985). 1995 Feb;78(2):394-402. doi: 10.1152/jappl.1995.78.2.394.
The effects of sensory neuropeptides on the airway responsiveness to acetylcholine (ACh) were investigated in normal nonsensitized rats. The airway responsiveness to inhaled ACh was significantly increased after treatment with neurokinin A (NKA; 0.001%) or substance P (SP; 0.01%) aerosol in the presence of the neutral endopeptidase (NEP) inhibitor. NKA had a more potent effect than SP. Interestingly, the intravenous treatment with NEP inhibitor alone also induced airway hyperresponsiveness (AHR) to inhaled ACh. This AHR was significantly attenuated by pretreatment with a nonselective NK-receptor antagonist, [D-Pro2,D-Trp7,9]SP, systemic capsaicin, or bilateral cervical vagotomy, indicating that decreased NEP activity results in accumulation of endogenous sensory neuropeptide(s) and enhancement of vagal reflex to cause AHR. The airway responsiveness to ACh of isolated left main bronchus was also increased after treatment with 10(-6) M NKA, but not SP, together with 10(-6) M phosphoramidon. This in vitro AHR to ACh induced by phosphoramidon plus NKA was significantly attenuated by pretreatment with 10(-6) M tetrodotoxin. These findings suggest that overaccumulated sensory neuropeptides, especially NKA, may enhance the probability of transmitter release, probably via NK2 receptors, and that the enhanced transmitter release might be involved in AHR in rats.
在正常未致敏大鼠中研究了感觉神经肽对气道对乙酰胆碱（ACh）反应性的影响。在中性内肽酶（NEP）抑制剂存在的情况下，用神经激肽A（NKA；0.001%）或P物质（SP；0.01%）气雾剂处理后，气道对吸入ACh的反应性显著增加。NKA的作用比SP更强。有趣的是，单独静脉注射NEP抑制剂也会诱导气道对吸入ACh的高反应性（AHR）。用非选择性NK受体拮抗剂[D-Pro2，D-Trp7，9]SP、全身辣椒素预处理或双侧颈迷走神经切断术可显著减轻这种AHR，表明NEP活性降低导致内源性感觉神经肽积累和迷走神经反射增强，从而引起AHR。用10（-6）M NKA（而非SP）与10（-6）M磷酰胺处理后，分离的左主支气管对ACh的气道反应性也增加。磷酰胺加NKA诱导的这种体外对ACh的AHR在用10（-6）M河豚毒素预处理后显著减轻。这些发现表明，过度积累的感觉神经肽，尤其是NKA，可能通过NK2受体增强递质释放的可能性，并且增强的递质释放可能与大鼠的AHR有关。
