DIFFERENCES IN THE DISTRIBUTION AND CHARACTERISTICS OF TACHYKININ NK1BINDING-SITES BETWEEN HUMAN AND GUINEA-PIG LUNG

1 The distribution and characteristics of tachykinin NK1 binding sites have been compared in human and guinea pig lung using quantitative in vitro receptor autoradiography with [I-125]-Bolton Hunter-labelled su bstance P ([I-125]-BH-SP). In addition, the effects on these sites of ovalbumin sensitization and challenge have been determined in guinea p ig lung. 2 [I-125]-BH-SP bound specifically and with high affinity to microvascular endothelium in both human and guinea pig lung, but to br onchial smooth muscle and pulmonary artery media in only guinea pig lu ng. 3 Specific binding of [!ISI]-BH-SP to guinea pig bronchial smooth muscle was positively correlated with airway diameter in the range 150 -800 mu m and was less dense in trachea than in main bronchi. 4 [I-125 ]-BH-SP binding was inhibited by tachykinins with rank orders of affin ity of SP > NKA > NKB (human microvessels) and SP>NKA=NKB (guinea pig bronchi and pulmonary arteries). NKA displayed a higher affinity for [ I-125]-BH-SP binding sites in human microvessels than in guinea pig ti ssues (P<0.0001), indicating differences in selectivity for tachykinin s between human and guinea pig NK1 receptors. 5 In both human and guin ea pig lung, [I-125]-BH-SP binding was inhibited by the specific tachy kinin receptor antagonists FK888 (NK1 selective antagonist) and FK224 (mixed NK1/NK2 antagonist), with FK888 displaying equal affinity to SP and > 500 times higher affinity than FK224. SP, NKA, NKB and FK888 ex hibited similar affinities for [I-125]-BH-SP binding sites in both gui nea pig arteries and bronchi. 6 Similar distributions, densities and c haracteristics of [I-125]-BH-SP binding sites were demonstrated in ova lbumin-sensitized and -challenged guinea-pig lung and in naive animals . 7 Differences in the distribution and characteristics of NK1 binding sites labelled with [I-125]-BH-SP between guinea pig and human lung s uggest limitations in the use of guinea pig models for studying roles of tachykinins in pulmonary disease. However, the similar microvascula r distributions of NK1 binding sites in human and guinea pig lung sugg est that the selective tachykinin receptor antagonists FK888 and FK224 may be useful in the management of airway inflammation in man.