Nieri P, Lazzeri N, Greco R, Breschi M C
Department of Psychiatry, Neurobiology, Pharmacology and Biotechnology, University of Pisa, Italy.
Immunopharmacology. 1998 Jun;39(3):235-42. doi: 10.1016/s0162-3109(98)00013-7.
Noise-exposure makes non-sensitized guinea pigs hyporesponsive to Acetylcholine (Ach), while in Ovalbumin (OA)-sensitized guinea pigs the responsiveness to the cholinergic mediator is not modified by acoustic stress (Nieri et al., 1996). The occurrence of bronchial hyporesponsiveness after acoustic stress in non-sensitized guinea pigs was verified also with histamine, obtaining a result similar to that observed with Ach. Moreover, the role of adenosine as modulator of the bronchial responsiveness to Ach after noise-exposure was assessed both in normal and in sensitized guinea pigs. In non-sensitized noise-exposed guinea pigs, the hyporesponsiveness to Ach was abolished by pretreatment of the animals with the peripheral A1/A2 antagonist 8-p-(sulfophenyl)theophylline (8-pSPT, 3 mg/kg i.v.) or with the A2-selective blocker 3,7-dimethyl-1-propargylxanthine (DMPX, 80 microg/kg i.v.) but not with the A1-selective antagonist Xanthine Amine Congener (XAC, 0.1 mg/kg i.v.). In sensitized guinea pigs, pretreatment with theophylline (25 mg/kg i.v.) makes noise-exposed animals again hyporesponsive to Ach, while no effect was obtained with the selective A1 and A2 antagonists employed. Also enprofylline (10 mg/kg i.v.), a phosphodiesterase inhibitor more potent than theophylline, does not modify the responsiveness to Ach in sensitized noise-exposed guinea pigs. The overall data presented suggest the involvement of the peripheral purinergic system in the regulation of airway reactivity after the stressful condition and indicate an altered functionality of this system as a consequence of sensitization. Furthermore, noise-exposure makes it possible to reveal in guinea pigs an opposite influence by theophylline on airway responsiveness to Ach, in sensitized, with respect to normal, animals.
噪声暴露会使未致敏的豚鼠对乙酰胆碱(Ach)反应性降低,而在卵清蛋白(OA)致敏的豚鼠中,声应激不会改变其对胆碱能介质的反应性(涅里等人,1996年)。在未致敏的豚鼠中,声应激后支气管反应性降低也通过组胺得到了证实,结果与用Ach观察到的相似。此外,还评估了腺苷在正常和致敏豚鼠噪声暴露后对支气管对Ach反应性的调节作用。在未致敏的噪声暴露豚鼠中,用外周A1/A2拮抗剂8-对-(磺苯基)茶碱(8-pSPT,3毫克/千克静脉注射)或A2选择性阻滞剂3,7-二甲基-1-丙炔基黄嘌呤(DMPX,80微克/千克静脉注射)预处理动物可消除对Ach的反应性降低,但用A1选择性拮抗剂黄嘌呤胺类似物(XAC,0.1毫克/千克静脉注射)则无效。在致敏豚鼠中,用茶碱(25毫克/千克静脉注射)预处理使噪声暴露动物再次对Ach反应性降低,而使用的选择性A1和A2拮抗剂则无此作用。比茶碱更有效的磷酸二酯酶抑制剂恩丙茶碱(10毫克/千克静脉注射)也不会改变致敏的噪声暴露豚鼠对Ach的反应性。所呈现的总体数据表明外周嘌呤能系统参与了应激状态后气道反应性的调节,并表明该系统的功能因致敏而改变。此外,噪声暴露使得在豚鼠中揭示出茶碱在致敏动物与正常动物中对气道对Ach反应性的相反影响成为可能。