Agrawal D K, Bergren D R, Byorth P J, Townley R G
Department of Internal Medicine, Creighton University School of Medicine, Omaha, Nebraska.
J Pharmacol Exp Ther. 1991 Oct;259(1):1-7.
Platelet-activating factor (PAF) is a potent mediator of inflammation and is a mediator which is known to cause airway hyperresponsiveness in human and experimental animals. However, the mechanism of action of PAF is not clear. In this study we examined the effect of methacholine upon specific airway resistance (SRaw) in guinea pigs and the ability of either isoproterenol or prostaglandin E2 to reverse this effect both before and after PAF administration at sub-bronchoactive doses in conscious guinea pigs as well as in isolated airway tissues. SRaw in conscious guinea pigs was monitored using a whole-body plethysmograph. In nonsensitized guinea pigs, a concentration of PAF (0.1 micrograms/ml), which by itself did not affect SRaw, potentiated the methacholine-induced increase in SRaw. In ovalbumin-sensitized animals, the response to methacholine was significantly greater as compared to the nonsensitized group. Prior administration of PAF did not potentiate the response to methacholine in ovalbumin-sensitized animals. In isolated tracheal rings and lung parenchymal strips of nonsensitized guinea pigs, preincubation of the tissue with 0.1 microM PAF decreased the sensitivity of isoproterenol to induce relaxation. However, in the ovalbumin-sensitized group of guinea pig tracheas or lung parenchymas, PAF did not reduce further the effect of isoproterenol to elicit relaxation. Furthermore, PAF did not alter the affinity or the density of beta adrenoceptors in guinea pig lung membranes. These data suggest that PAF may potentiate the responses to bronchoconstrictors and desensitize the responses to bronchodilators in a nonspecific manner. This may be a mechanism underlying PAF-induced airway hyperresponsiveness in asthma.
血小板活化因子（PAF）是一种强效的炎症介质，是已知可在人和实验动物中引起气道高反应性的介质。然而，PAF的作用机制尚不清楚。在本研究中，我们检测了乙酰甲胆碱对清醒豚鼠特异性气道阻力（SRaw）的影响，以及异丙肾上腺素或前列腺素E2在豚鼠清醒状态下以及离体气道组织中给予亚支气管活性剂量的PAF前后逆转这种影响的能力。使用全身体积描记器监测清醒豚鼠的SRaw。在未致敏的豚鼠中，浓度为0.1微克/毫升的PAF本身不影响SRaw，但能增强乙酰甲胆碱诱导的SRaw增加。在卵清蛋白致敏的动物中，与未致敏组相比，对乙酰甲胆碱的反应明显更大。预先给予PAF并不能增强卵清蛋白致敏动物对乙酰甲胆碱的反应。在未致敏豚鼠的离体气管环和肺实质条带中，用0.1微摩尔/升PAF对组织进行预孵育会降低异丙肾上腺素诱导舒张的敏感性。然而，在卵清蛋白致敏的豚鼠气管或肺实质组中，PAF并没有进一步降低异丙肾上腺素引起舒张的作用。此外，PAF并没有改变豚鼠肺膜中β肾上腺素能受体的亲和力或密度。这些数据表明，PAF可能以非特异性方式增强对支气管收缩剂的反应并使对支气管扩张剂的反应脱敏。这可能是PAF诱导哮喘气道高反应性的潜在机制。
