Evangelista S, Paoli S, Giachetti A, Manzini S
Department of Pharmacology, Istituto Farmacobiologico Malesci S.p.A., Firenze, Italy.
Neuropeptides. 1997 Feb;31(1):65-70. doi: 10.1016/s0143-4179(97)90022-6.
Plasma protein extravasation in the upper airways of anesthetized guinea pigs was measured with the FITC (Fluorescein isothiocyanate)-dextran technique. The effect of selective tachykinin (NK1 and NK2) receptor agonists and antagonists, capsaicin or antigen was studied. The tachykinin NK1 receptor agonist, [Sar9]substance P sulfone, induced an increase in FITC-dextran extravasation which was blocked by the nasal application (30-100 nmol/kg) of the tachykinin NK1 receptor antagonist FK888, but not by 1 micromol/kg of the tachykinin NK2 receptor antagonist, MEN10,627. The tachykinin NK2 receptor agonist, [betaAla8]neurokinin A-(4-10), had no effect on dye leakage. FK888 (30 nmol/kg intranasal) abolished the increase in the tracer recovery induced both by antigen and capsaicin. Conversely, the intranasal administration of MEN10,627 (0.1-1.0 micromol/kg) significantly reduced capsaicin-induced and only marginally inhibited antigen-induced increase in plasma protein extravasation. Pretreatment with the neutral endopeptidase inhibitor, phosphoramidon, increased the effect of all inflammatory agents. These findings show that the plasma extravasation of the upper airways induced by exogenous or endogenous tachykinins is primarily mediated by tachykinin NK1 receptors. This inflammatory response could be controlled by locally applied tachykinin NK1 receptor antagonist.
采用异硫氰酸荧光素（FITC）-葡聚糖技术测定麻醉豚鼠上呼吸道的血浆蛋白外渗情况。研究了选择性速激肽（NK1和NK2）受体激动剂和拮抗剂、辣椒素或抗原的作用。速激肽NK1受体激动剂[Sar9]P物质砜可导致FITC-葡聚糖外渗增加，鼻腔应用速激肽NK1受体拮抗剂FK888（30 - 100 nmol/kg）可阻断这一作用，但1 μmol/kg的速激肽NK2受体拮抗剂MEN10,627则无此作用。速激肽NK2受体激动剂[βAla8]神经激肽A-(4 - 10)对染料渗漏无影响。FK888（鼻腔内给药30 nmol/kg）可消除抗原和辣椒素引起的示踪剂回收率增加。相反，鼻腔内给予MEN10,627（0.1 - 1.0 μmol/kg）可显著降低辣椒素诱导的血浆蛋白外渗增加，而对抗原诱导的增加仅有轻微抑制作用。用中性内肽酶抑制剂磷酰胺预处理可增强所有炎症介质的作用。这些发现表明，外源性或内源性速激肽诱导的上呼吸道血浆外渗主要由速激肽NK1受体介导。这种炎症反应可通过局部应用速激肽NK1受体拮抗剂来控制。
