血小板活化因子对犬气道兴奋性神经效应器传递的影响。

Effects of PAF on excitatory neuro-effector transmission in dog airways.

作者信息

Tashiro K, Xie Z, Ito Y

机构信息

Department of Pharmacology, Faculty of Medicine, Kyushu University, Fukuoka, Japan.

出版信息

Br J Pharmacol. 1992 Dec;107(4):956-63. doi: 10.1111/j.1476-5381.1992.tb13391.x.

DOI:10.1111/j.1476-5381.1992.tb13391.x

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC1907945/

Abstract

Effects of PAF on excitatory neuro-effector transmission in smooth muscle cells of mucosa-free trachea and epithelium-intact bronchiole of the dog were investigated, by isometric tension recording, microelectrode and double sucrose-gap methods. 2. PAF (10(-11)-10(-7) M) dose-dependently enhanced the amplitude of contraction evoked by repetitive field stimulations (10 stimuli at 20 Hz) in both tracheal and bronchiolar tissues. At higher concentrations PAF (> 10(-8) M) increased the amplitude of contraction to a greater extent in the bronchiole than in the trachea. 3. In both muscle tissues, in parallel to the amplitude of contraction, PAF markedly enhanced the amplitude of excitatory junction potentials (e.j.ps) evoked by a single field stimulation in a dose-dependent manner, with no change in the resting membrane potential or input membrane resistance of the smooth muscle cells. PAF (5 x 10(-7) M) enhanced the amplitude of e.j.p. to a greater extent in the bronchiole than in the trachealis. In contrast, lyso-PAF (10(-10)-10(-7) M) showed no effect on e.j.p. amplitude in bronchiolar tissues. At a high concentration (10(-7) M) lyso-PAF slightly enhanced the e.j.p. amplitude in tracheal tissue, however the lyso-PAF induced stimulation of e.j.p. amplitude in the trachea was small compared to that of PAF. 4. PAF (10(-7) M) had no effect on the membrane depolarization induced by acetylcholine (ACh, 10(-9)-10(-5) M) and carbachol (10(-9)-10(-5) M) in tracheal smooth muscle cells. 5. The PAF-antagonists CV3988 (5 x i0-7 M) or WEB2086 (5 x 10-7 M) significantly enhanced the e.j.p. amplitude themselves, PAF (5 x 10-8 M) further enhanced the ej.p. amplitude in the presence of WEB2086 (5 x l0-7 M) but not CV3988 (5 x 10-7 M). In contrast, the new PAF-antagonist, E 6123(5 x l0-8 M), did not affect the ej.p. amplitude itself, and completely inhibited the increase in ej.p. amplitude caused by 5 x 10-8 M PAF. On the other hand, in the presence of the Hi-antagonist,mepyramine, PAF (5 X 10-8 M) further enhanced the ej.p. amplitude.6. The leukotriene synthesis inhibitor AA-861 (10-6 M) or leukotriene antagonist ONO1078 (10-7 M)inhibited the increase in ej.p. amplitude caused by 5 X 10-8 M PAF, respectively.7. In the presence of AA-861 (10-6 M), leukotriene B4 (LTB4, 10-' M) or LTD4 (10-8 M) slightly, and LTC4 (10- M) markedly enhanced the ej.p. amplitude. In contrast, LTE4 (10-8 M) significantly suppressed the e.j.p. amplitude.8. PAF (5 x 10-8 M) attenuated the depression phenomena of ej.ps observed during double stimulus experiments at different time intervals (5-10 s), but had no effect on the summation of ej.ps during repetitive field stimulation at a high frequency (20 Hz) in the trachealis.9. These results indicate that PAF potentiates excitatory neuro-effector transmission mainly through stimulating the release of lipoxygenase products, mainly LTC4 in the dog airway smooth muscle tissues.

摘要

采用等长张力记录法、微电极法和双蔗糖间隙法，研究了血小板活化因子（PAF）对犬无黏膜气管平滑肌细胞和完整上皮细支气管兴奋性神经效应器传递的影响。2. PAF（10⁻¹¹ - 10⁻⁷M）剂量依赖性地增强了气管和细支气管组织中重复场刺激（20Hz下10次刺激）诱发的收缩幅度。在较高浓度时，PAF（>10⁻⁸M）在细支气管中比在气管中更能增加收缩幅度。3. 在两种肌肉组织中，与收缩幅度平行，PAF以剂量依赖性方式显著增强单场刺激诱发的兴奋性接头电位（e.j.ps）幅度，而平滑肌细胞的静息膜电位或输入膜电阻无变化。PAF（5×10⁻⁷M）在细支气管中比在气管肌中更能增强e.j.p.幅度。相反，溶血PAF（10⁻¹⁰ - 10⁻⁷M）对细支气管组织中的e.j.p.幅度无影响。在高浓度（10⁻⁷M）时，溶血PAF略微增强气管组织中的e.j.p.幅度，然而与PAF相比，溶血PAF在气管中诱导的e.j.p.幅度刺激较小。4. PAF（10⁻⁷M）对气管平滑肌细胞中乙酰胆碱（ACh，10⁻⁹ - 10⁻⁵M）和卡巴胆碱（10⁻⁹ - 10⁻⁵M）诱导的膜去极化无影响。5. PAF拮抗剂CV3988（5×10⁻⁷M）或WEB2086（5×10⁻⁷M）本身显著增强e.j.p.幅度，在存在WEB2086（5×10⁻⁷M）而非CV3988（5×10⁻⁷M）时，PAF（5×10⁻⁸M）进一步增强e.j.p.幅度。相反，新型PAF拮抗剂E 6123（5×10⁻⁸M）本身不影响e.j.p.幅度，并完全抑制5×10⁻⁸M PAF引起的e.j.p.幅度增加。另一方面，在存在组胺拮抗剂美吡拉敏时，PAF（5×10⁻⁸M）进一步增强e.j.p.幅度。6. 白三烯合成抑制剂AA - 861（10⁻⁶M）或白三烯拮抗剂ONO1078（10⁻⁷M）分别抑制5×10⁻⁸M PAF引起的e.j.p.幅度增加。7. 在存在AA - 861（10⁻⁶M）时，白三烯B4（LTB4，10⁻⁷M）或LTD4（10⁻⁸M）轻微增强，而LTC4（10⁻⁷M）显著增强e.j.p.幅度。相反，LTE4（10⁻⁸M）显著抑制e.j.p.幅度。8. PAF（5×10⁻⁸M）减弱了在不同时间间隔（5 - 10s）双刺激实验中观察到的e.j.ps的抑制现象，但对气管肌高频（20Hz）重复场刺激期间的e.j.ps总和无影响。9. 这些结果表明，PAF主要通过刺激脂氧合酶产物（主要是犬气道平滑肌组织中的LTC4）的释放来增强兴奋性神经效应器传递。