Fernandes L B, Knight D A, Rigby P J, Spina D, Paterson J W, Goldie R G
Department of Pharmacology, University of Western Australia, Perth, Nedlands.
Eur J Pharmacol. 1988 Nov 22;157(2-3):135-45. doi: 10.1016/0014-2999(88)90376-7.
Exposure to (-)-isoprenaline (25 microM, 1 h) caused a stereoselective, time and concentration-related decrease in smooth muscle beta 2-adrenoceptor function in guinea-pig trachea. Furthermore, tracheal relaxant responsiveness to the beta-adrenoceptor agonists (+/-)-fenoterol and (-)-noradrenaline was reduced, while that to theophylline and nitroprusside was unaffected. Responsiveness to forskolin was marginally but significantly reduced. Indomethacin, a cyclooxygenase inhibitor and mepacrine, an inhibitor of phospholipid turnover, had no significant effect on the extent of isoprenaline-induced desensitization. Conversely, cortisol (25 microM) significantly reduced desensitization and enhanced the rate of spontaneous recovery of responsiveness to isoprenaline. Desensitization was not accompanied by a reduction in the density of beta-adrenoceptors in the trachea, as assessed by binding and light microscopic autoradiography using [125I]iodocyanopindolol [( 125I]CYP). Thus, desensitization was probably caused primarily by beta-adrenoceptor/adenyl cyclase uncoupling. This model may be useful in investigations of the effect of glucocorticoids on the beta-adrenoceptor dysfunction recognized in severe asthma.
暴露于（-）-异丙肾上腺素（25微摩尔，1小时）导致豚鼠气管平滑肌β2-肾上腺素能受体功能出现立体选择性、时间和浓度相关的下降。此外，气管对β-肾上腺素能受体激动剂（±）-非诺特罗和（-）-去甲肾上腺素的舒张反应性降低，而对茶碱和硝普钠的反应性未受影响。对福斯可林的反应性略有但显著降低。环氧化酶抑制剂吲哚美辛和磷脂周转抑制剂米帕林对异丙肾上腺素诱导的脱敏程度无显著影响。相反，皮质醇（25微摩尔）显著降低脱敏作用并提高对异丙肾上腺素反应性的自发恢复速率。通过使用[125I]碘氰吲哚洛尔[（125I）CYP]进行结合和光学显微镜放射自显影评估，脱敏并未伴随着气管中β-肾上腺素能受体密度的降低。因此，脱敏可能主要是由β-肾上腺素能受体/腺苷酸环化酶解偶联引起的。该模型可能有助于研究糖皮质激素对严重哮喘中公认的β-肾上腺素能受体功能障碍的影响。
