Cadieux A, Monast N P, Pomerleau F, Fournier A, Lanoue C
Department of Pharmacology, Faculty of Medicine, University of Sherbrooke, INRS-Santé, University of Quebec, Pointe Claire, Quebec, Canada.
Am J Respir Crit Care Med. 1999 Jan;159(1):235-43. doi: 10.1164/ajrccm.159.1.9711031.
Calcitonin gene-related peptide (CGRP), a neuropeptide released from sensory nerves during axonal reflexes, has strong bronchoprotector properties in rat isolated airways. In this study, we examined this ability of CGRP to prevent agonist-induced contraction in guinea pig and human airways and determined whether inflammatory reaction affects its function. CGRP administered intravenously (0.38 to 114 microgram/kg) in anesthesized guinea pig had no effect per se on airway resistance but caused a dose-related inhibition of substance P (SP; 13.5 microgram/kg)-induced bronchoconstriction (60% at 114 microgram/kg). Similarly, CGRP (10(-)9 to 10(-)6 M) prevented in a concentration-dependent manner the contraction elicited by SP (5 x 10(-)8 M) in guinea pig isolated main bronchi and parenchymal strips, the inhibition caused by CGRP being more pronounced in distal than in proximal airways (47 and 20%, respectively, at 10(-)6 M). The breaking effect of CGRP on SP-induced constriction was however significantly reduced (p < 0.05) in guinea pig actively sensitized to ovalbumin (OA) and the loss in its potency was of similar magnitude (> 40%) whether it was administered in vivo or in vitro. A same phenomenon was observed in human isolated peripheral bronchi. CGRP (10(-)6 M) reduced by more than 75% the extent of the contraction evoked by 10(-)6 M of carbamylcholine and its protector effect was totally abolished in bronchi showing clear morphological manifestation of inflammatory reaction. It is concluded that CGRP acts as a potent bronchoprotector agent on both guinea pig and human airways but its ability to limit the extent of airway responsiveness is strongly impaired in inflammatory conditions.
降钙素基因相关肽（CGRP）是轴突反射过程中从感觉神经释放的一种神经肽，在大鼠离体气道中具有很强的支气管保护特性。在本研究中，我们检测了CGRP预防豚鼠和人气道中激动剂诱导收缩的能力，并确定炎症反应是否会影响其功能。在麻醉的豚鼠中静脉注射CGRP（0.38至114微克/千克）本身对气道阻力没有影响，但对P物质（SP；13.5微克/千克）诱导的支气管收缩产生剂量相关的抑制作用（114微克/千克时为60%）。同样，CGRP（10⁻⁹至10⁻⁶摩尔/升）以浓度依赖的方式预防了SP（5×10⁻⁸摩尔/升）在豚鼠离体主支气管和平滑肌条中引起的收缩，CGRP引起的抑制在远端气道比近端气道更明显（10⁻⁶摩尔/升时分别为47%和20%）。然而，在对卵清蛋白（OA）主动致敏的豚鼠中，CGRP对SP诱导收缩的阻断作用显著降低（p<0.05），无论在体内还是体外给药，其效力损失幅度相似（>40%）。在人离体外周支气管中也观察到了同样的现象。CGRP（10⁻⁶摩尔/升）使10⁻⁶摩尔/升氨甲酰胆碱引起的收缩程度降低了75%以上，并且在显示出明显炎症反应形态学表现的支气管中，其保护作用完全丧失。结论是，CGRP在豚鼠和人气道中均作为一种有效的支气管保护剂，但在炎症条件下，其限制气道反应性程度的能力会受到严重损害。
