Neurokinins Induce Relaxation of Human Pulmonary Vessels Through Stimulation of Endothelial NK1 Receptors
Neurokinins Induce Relaxation of Human Pulmonary Vessels Through Stimulation of Endothelial NK1 Receptors
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神经激肽通过刺激内皮 NK1 受体诱导人肺血管舒张
DOI：
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发表时间：
2003
影响因子：
3
通讯作者：
P. Devillier
中科院分区：
文献类型：
--
作者：
H. Mechiche;A. Koroglu;L. Candenas;F. Pinto;P. Birembaut;M. Bardou;J. Elaerts;P. Devillier
神经激肽和神经激肽受体选择性激动剂对人叶内肺血管的作用已被研究。P物质（SP）和选择性NK 1受体激动剂[Sar 9 Met（O2）11]SP均能浓度依赖性地舒张苯肾上腺素预收缩的肺血管。动脉制剂中SP和[Sar 9 Met（O2）11]SP的平均负log（M）EC 50值分别为8.6和8.9，静脉制剂中分别为8.9和8.6。NK 1受体拮抗剂SR 140333可阻断[Sar 9 Met（O2）11]SP的舒张作用。第二次应用[Sar 9 Met（O2）11]SP的弛豫明显减少，表明NK 1受体快速脱敏。用乙酰胆碱时未观察到这种脱敏作用。选择性NK 2受体激动剂[Nle 10]NKA和选择性NK 3受体激动剂[MePhe 7]NKB既不引起肺血管收缩也不引起肺血管舒张。NK 1受体介导的舒张被取消，通过去除内皮细胞或由NG-硝基-L-精氨酸和吲哚美辛的组合，而每个化合物产生部分抑制作用。用乙酰胆碱观察到类似的结果。NK 1受体的阳性染色仅见于内皮细胞。逆转录-聚合酶链反应检测到NK 1受体的信使RNA，而没有检测到NK 2或NK 3受体的信使RNA。总之，人肺动脉和静脉表达内皮NK 1受体，其通过环氧合酶和一氧化氮活性的组合介导松弛，并经受快速耐受。
The effects of neurokinins and neurokinin receptor selective agonists have been investigated on human intralobar pulmonary vessels. Substance P (SP) and [Sar9Met(O2)11]SP, a selective NK1 receptor agonist, induced concentration-dependent relaxation of pulmonary vessels precontracted with phenylephrine. The mean negative log (M) EC50 values for SP and [Sar9Met(O2)11]SP were 8.6 and 8.9, respectively, on arterial preparations and 8.9 and 8.6, respectively, on venous preparations. Relaxations to [Sar9Met(O2)11]SP were abolished by the NK1 receptor antagonist SR140333. The relaxations to a second application of [Sar9Met(O2)11]SP were markedly reduced, suggesting a rapid desensitization of the NK1 receptor. Such desensitization was not observed with acetylcholine. The selective NK2 receptor agonist, [Nle10]NKA, and the selective NK3 receptor agonist, [MePhe7]NKB, caused neither contractions nor relaxations of pulmonary vessels. The NK1 receptor-mediated relaxations were abolished by removing the endothelium or by a combination of NG-nitro-L-arginine and indomethacin, whereas each compound exerted a partial inhibitory effect. Similar results were observed with acetylcholine. Positive immunostaining for NK1 receptors was only found in the endothelium. Reverse transcription-polymerase chain reaction detected messenger RNA for NK1 receptors without any detection of messenger RNA for NK2 or NK3 receptors. In conclusion, human pulmonary arteries and veins express endothelial NK1 receptors that mediate relaxation through a combination of cyclooxygenase and nitric oxide activities and are subjected to rapid tachyphylaxis.
DOI：
10.1016/0006-291x(91)91704-g
发表时间：
1991-09
影响因子：
3.1
作者：
Yasuo Takeda;K. B. Chou;J. Takeda;B. Sachais;J. E. Krause
通讯作者：
Yasuo Takeda;K. B. Chou;J. Takeda;B. Sachais;J. E. Krause
影响因子：
3.3
作者：
GRADY, EF;GARLAND, AM;BUNNETT, NW
通讯作者：
BUNNETT, NW
完整细胞中人 P 物质受体的快速激动剂依赖性磷酸化和佛波酯介导的磷酸化之间差异的表征。
DOI：
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发表时间：
1999
期刊：
Molecular pharmacology.
影响因子：
--
作者：
Roush,ED;Warabi,K;Kwatra,MM
通讯作者：
Kwatra,MM