Gao X P, Robbins R A, Snider R M, Lowe J, Rennard S I, Anding P, Rubinstein I
Department of Internal Medicine, University of Nebraska Medical Center, Omaha 68198.
Am J Physiol. 1993 Aug;265(2 Pt 2):H593-8. doi: 10.1152/ajpheart.1993.265.2.H593.
The purpose of this study was to determine the receptor subtype(s) that mediates tachykinin-induced neurogenic plasma extravasation in the hamster cheek pouch. Changes in microvascular clearance were quantified by counting the number of leaky sites and calculating the clearance of fluorescein isothiocyanate-dextran [mol wt 70,000 (Dextran 70)] during suffusion of the cheek pouch with substance P, neurokinin A, neurokinin B, and capsaicin. Suffusion of substance P, capsaicin, and neurokinin A, but not neurokinin B, was associated with a significant concentration-dependent increase in leaky site formation and clearance of fluorescein isothiocyanate-Dextran 70 (P < 0.05). However, the responses to substance P and capsaicin were significantly greater than those to neurokinin A. Pretreatment with the selective, nonpeptide NK1 receptor antagonist, CP-96,345, significantly attenuated substance P- and capsaicin-induced but not neurokinin A-induced responses (P < 0.05). These effects were specific, since the 2R,3R enantiomer, CP-96,344, was inactive, and CP-96,345 had no significant effect on adenosine-induced responses. We conclude that, in the hamster cheek pouch, NK1 receptors are the predominant receptors that mediate neurogenic plasma extravasation.
本研究的目的是确定介导速激肽诱导的仓鼠颊囊神经源性血浆外渗的受体亚型。通过在颊囊灌注P物质、神经激肽A、神经激肽B和辣椒素期间计数渗漏部位的数量并计算异硫氰酸荧光素-葡聚糖[分子量70,000（葡聚糖70）]的清除率，对微血管清除率的变化进行定量。灌注P物质、辣椒素和神经激肽A（而非神经激肽B）与渗漏部位形成和异硫氰酸荧光素-葡聚糖70清除率的显著浓度依赖性增加相关（P<0.05）。然而，对P物质和辣椒素的反应明显大于对神经激肽A的反应。用选择性非肽NK1受体拮抗剂CP-96,345预处理可显著减弱P物质和辣椒素诱导的反应，但不减弱神经激肽A诱导的反应（P<0.05）。这些作用具有特异性，因为2R,3R对映体CP-96,344无活性，且CP-96,345对腺苷诱导的反应无显著影响。我们得出结论，在仓鼠颊囊中，NK1受体是介导神经源性血浆外渗的主要受体。
