Yang B, Schlosser R J, McCaffrey T V
Department of Otorhinolaryngology, Mayo Clinic, Rochester, Minnesota 55905, USA.
Am J Physiol. 1996 May;270(5 Pt 1):L745-51. doi: 10.1152/ajplung.1996.270.5.L745.
This study investigated the effects of methacholine and terbutaline on the ciliary beat frequency (CBF) of upper airway epithelium. The CBF of cultured human adenoid explants was measured using microphotometry. Methacholine (10(-6) M) and terbutaline (10(-6)M) increased CBF a maximum of 23.0 +/- 1.8% (P < 0.001) and 16.5 +/- 2.3% (P < 0.001). Inhibition of endogenous nitric oxide (NO) production by nitro-L-arginine methyl ester (L-NAME) (10(-6) M) abolished the effects of methacholine in L-arginine-free medium (P < 0.008). This inhibition was reversed by addition of L-arginine. There was no inhibition of terbutaline-induced ciliostimulation by L-NAME (P < 0.5). KT-5823 (10(-6)M), a guanosine 3',5'-cyclic monophosphate (cGMP) kinase inhibitor, significantly inhibited the effects of methacholine (P < 0.0001), but not terbutaline (P > 0.15). H-89 (10(-6) M), a cAMP kinase inhibitor, significantly inhibited terbutaline-induced ciliostimulation (P < 0.0001), but not methacholine-induced ciliostimulation (P > 0.05). Diclofenac (10(-6) M), a cyclooxygenase inhibitor, significantly inhibited the effects of methacholine (P < 0.0007) but had no effect on terbutaline-induced ciliostimulation (P > 0.05). These findings suggest that the CBF of upper airway epithelium is modulated through at least two distinct pathways. The beta 2-adrenoceptor produces ciliary stimulation by a pathway involving increased intracellular cAMP levels, while the muscarinic receptor increases CBF by a mechanism involving production of prostaglandins, NO, and cGMP.
本研究调查了乙酰甲胆碱和特布他林对上呼吸道上皮细胞纤毛摆动频率（CBF）的影响。使用显微光度测定法测量培养的人腺样体组织块的CBF。乙酰甲胆碱（10⁻⁶ M）和特布他林（10⁻⁶ M）使CBF分别最大增加23.0±1.8%（P<0.001）和16.5±2.3%（P<0.001）。在无L-精氨酸的培养基中，硝基-L-精氨酸甲酯（L-NAME）（10⁻⁶ M）抑制内源性一氧化氮（NO）生成后，消除了乙酰甲胆碱的作用（P<0.008）。添加L-精氨酸可逆转这种抑制作用。L-NAME对特布他林诱导的纤毛刺激无抑制作用（P<0.5）。鸟苷3',5'-环磷酸（cGMP）激酶抑制剂KT-5823（10⁻⁶ M）显著抑制乙酰甲胆碱的作用（P<0.0001），但对特布他林无抑制作用（P>0.15）。环磷酸腺苷（cAMP）激酶抑制剂H-89（10⁻⁶ M）显著抑制特布他林诱导的纤毛刺激（P<0.0001），但对乙酰甲胆碱诱导的纤毛刺激无抑制作用（P>0.05）。环氧化酶抑制剂双氯芬酸（10⁻⁶ M）显著抑制乙酰甲胆碱的作用（P<0.0007），但对特布他林诱导的纤毛刺激无影响（P>0.05）。这些发现表明，上呼吸道上皮细胞的CBF至少通过两条不同途径进行调节。β₂肾上腺素能受体通过涉及细胞内cAMP水平升高的途径产生纤毛刺激，而毒蕈碱受体通过涉及前列腺素、NO和cGMP生成的机制增加CBF。
