Racké K, Bähring J, Langer C, Bräutigam M, Wessler I
Departments of Pharmacology, University of Frankfurt, Germany.
Am Rev Respir Dis. 1992 Nov;146(5 Pt 1):1182-6. doi: 10.1164/ajrccm/146.5_Pt_1.1182.
Prostanoids, of epithelial origin, are known as modulators of several processes in the airways. The present study examined whether prostanoids are involved in the local control of sympathetic neurotransmission. The release of endogenous norepinephrine from rat isolated tracheae was evoked by electrical field stimulation (3 Hz, 540 pulses) in the presence of yohimbine, desipramine, and tyrosine. In different series of experiments, indomethacin (3 mumol/L) increased the evoked release of endogenous norepinephrine by 70 to 80%. In the presence of indomethacin, prostaglandin E2 (PGE2) and several prostanoid receptor agonists inhibited the evoked release of norepinephrine in a concentration-dependent manner, maximally by 60 to 70%. According to the concentration producing 35% inhibition of norepinephrine release (half-maximal effect), the following rank order of potencies was observed (EC35): nocloprost (8 nmol/L), sulprostone (30 nmol/L), PGE2 (308 nmol/L), iloprost (2 mumol/L), and U46619 (> 10 mumol/L). The EP1 receptor antagonist AH 6809 (3 mumol/L) had no effect on the evoked norepinephrine release and did not affect the inhibitory effect of 1 mumol/L of sulprostone. In the absence of indomethacin, the inhibitory effect of PGE2 was similar to that observed in the presence of indomethacin. After removal of the epithelium, the evoked norepinephrine release was markedly reduced. However, no significant effect of indomethacin was observed in epithelium-denuded tracheae. In conclusion, norepinephrine release in the rat trachea is inhibited via prostaglandin receptors that have the pharmacologic characteristics of the EP3 subtype. Endogenous eicosanoids, most likely of epithelial origin, are involved in the local control of the release of norepinephrine.
前列腺素由上皮细胞产生，是气道多种生理过程的调节因子。本研究旨在探讨前列腺素是否参与交感神经传递的局部调控。在育亨宾、地昔帕明和酪氨酸存在的情况下，通过电场刺激（3Hz，540个脉冲）诱发大鼠离体气管释放内源性去甲肾上腺素。在不同系列的实验中，吲哚美辛（3μmol/L）使内源性去甲肾上腺素的诱发释放增加了70%至80%。在吲哚美辛存在的情况下，前列腺素E2（PGE2）和几种前列腺素受体激动剂以浓度依赖的方式抑制去甲肾上腺素的诱发释放，最大抑制率为60%至70%。根据产生35%去甲肾上腺素释放抑制作用的浓度（半数最大效应），观察到以下效价顺序（EC35）：诺克洛普（8nmol/L）、舒前列素（30nmol/L）、PGE2（308nmol/L）、伊洛前列素（2μmol/L）和U46619（>10μmol/L）。EP1受体拮抗剂AH 6809（3μmol/L）对诱发的去甲肾上腺素释放没有影响，也不影响1μmol/L舒前列素的抑制作用。在没有吲哚美辛的情况下，PGE2的抑制作用与在吲哚美辛存在时观察到的相似。去除上皮后，诱发的去甲肾上腺素释放明显减少。然而，在去上皮的气管中未观察到吲哚美辛的显著作用。总之，大鼠气管中去甲肾上腺素的释放通过具有EP3亚型药理学特征的前列腺素受体受到抑制。内源性类花生酸，很可能来源于上皮细胞，参与去甲肾上腺素释放的局部调控。
