Hua X Y, Yaksh T L
Department of Anesthesiology, University of California, San Diego, La Jolla 92093-0818.
J Neurosci. 1993 May;13(5):1947-53. doi: 10.1523/JNEUROSCI.13-05-01947.1993.
The effects of inflammatory substances, bradykinin (BK), 5-HT, and histamine (HIS), on the release of calcitonin gene-related peptide (CGRP) from the peripheral terminals of sensory afferents in the rat trachea were examined ex vivo. With intralumenal perfusion, the isolated rat trachea displays low but measurable secretion of CGRP (32 +/- 4.6 fmol/10 min fraction). The addition of BK (10(-6) to 10(-4) M) to the superfusate resulted in an immediate, concentration-dependent increase in the level of CGRP (5-30-fold increase above baseline) in the perfusates, and this effect showed a concentration-dependent tachyphylaxis. [Des-Arg10]-kallidin, a B1 receptor agonist, at concentrations of up to 10(-4) M did not induce any significant increase in CGRP outflow from the rat trachea. HIS at 10(-4) M caused a modest but progressive augmentation in the release of CGRP. 5-HT at 10(-4) M had no effect upon the resting efflux of CGRP, but at a concentration of 10(-6) M significantly enhanced the release of CGRP evoked by capsaicin (10(-6) M). Similar conditioning studies carried out with HIS and BK showed no augmentation. BK-evoked CGRP efflux was significantly inhibited by [D-Arg0, Hyp3, Thi5,8, D-Phe7]-BK (B2 antagonist) and indomethacin. While [Des-Arg9, Leu8]-BK (B1 antagonist) also caused a reduction of BK-induced release, its effect did not reach statistical significance.(ABSTRACT TRUNCATED AT 250 WORDS)
采用离体实验研究了炎性物质缓激肽（BK）、5-羟色胺（5-HT）和组胺（HIS）对大鼠气管感觉传入神经外周终末降钙素基因相关肽（CGRP）释放的影响。通过腔内灌注，分离的大鼠气管可分泌少量但可检测到的CGRP（32±4.6 fmol/10分钟馏分）。向灌流液中添加BK（10⁻⁶至10⁻⁴ M）可导致灌流液中CGRP水平立即出现浓度依赖性升高（比基线升高5至30倍），且该效应呈现浓度依赖性快速耐受。[去精氨酸¹⁰]-胰激肽，一种B1受体激动剂，浓度高达10⁻⁴ M时，未引起大鼠气管CGRP流出量显著增加。10⁻⁴ M的HIS可引起CGRP释放适度但逐渐增加。10⁻⁴ M的5-HT对CGRP的静息流出量无影响，但浓度为10⁻⁶ M时可显著增强辣椒素（10⁻⁶ M）诱发的CGRP释放。用HIS和BK进行的类似预处理研究未显示增强作用。BK诱发的CGRP流出量被[D-精氨酸⁰，Hyp³，Thi⁵,⁸，D-苯丙氨酸⁷]-BK（B2拮抗剂）和吲哚美辛显著抑制。虽然[去精氨酸⁹，亮氨酸⁸]-BK（B1拮抗剂）也可使BK诱导的释放减少，但其作用未达到统计学意义。（摘要截短于250字）
