Carraway R E, Cochrane D E, Salmonsen R, Muraki K, Boucher W
Department of Physiology, University of Massachusetts Medical School, Worcester 01650.
Peptides. 1991 Sep-Oct;12(5):1105-11. doi: 10.1016/0196-9781(91)90066-x.
The IV injection of neurotensin (NT) into anesthetized rats produced a marked increase in hematocrit, labored breathing and peripheral blood stasis with cyanosis. This effect could also be produced by the NT-related peptides, neuromedin-N and xenopsin; however, it was not observed when nine other biologically active peptides, including bradykinin and substance P, were tested. Associated with these responses were increases in the plasma levels of histamine (measured radioenzymatically) and the leukotrienes, LTB4, LTC4, LTD4, and LTE4 (measured by RIA and HPLC). The increment in hematocrit after varying doses of NT correlated to the increase in plasma levels of LTC4. Histamine and LTC4 were both capable of elevating hematocrit when given IV; however, LTC4 was approximately 1000 times more potent than histamine and active doses of histamine elevated LTC4 levels. Furthermore, the effects of NT on plasma LTC4 and hematocrit were reduced by pretreating animals with antagonists to histamine and serotonin. Pretreatment with the specific mast cell degranulating agent, compound 48/80, also blocked NT's ability to elevate plasma levels of histamine, LTB4 and LTC4 and prevented the increased hematocrit and cyanosis. These results indicate that NT-related peptides are very potent and specific stimulators of leukotriene release and that this action is mediated by mast cells and associated with loss of plasma volume and blood stasis. A working hypothesis is that histamine, released from mast cells in response to NT, stimulates LTC4 production by other cells.
给麻醉大鼠静脉注射神经降压素（NT）可导致血细胞比容显著升高、呼吸费力以及外周血淤血伴发绀。神经降压素相关肽神经介素 - N和异速肽也可产生这种效应；然而，在测试包括缓激肽和P物质在内的其他九种生物活性肽时未观察到这种效应。与这些反应相关的是血浆组胺水平（采用放射酶法测定）以及白三烯LTB4、LTC4、LTD4和LTE4水平（采用放射免疫分析法和高效液相色谱法测定）升高。不同剂量的神经降压素作用后血细胞比容的增加与血浆LTC4水平的升高相关。静脉注射组胺和LTC4均能升高血细胞比容；然而，LTC4的效力约为组胺的1000倍，且组胺的有效剂量可提高LTC4水平。此外，用组胺和5 - 羟色胺拮抗剂预处理动物可减弱神经降压素对血浆LTC4和血细胞比容的作用。用特异性肥大细胞脱颗粒剂化合物48/80预处理也可阻断神经降压素升高血浆组胺、LTB4和LTC4水平的能力，并防止血细胞比容升高和发绀。这些结果表明，神经降压素相关肽是白三烯释放的非常强效且特异的刺激剂，这种作用由肥大细胞介导，并与血浆容量减少和血液淤滞有关。一个可行的假说是，肥大细胞响应神经降压素释放组胺，刺激其他细胞产生LTC4。
