AUTORADIOGRAPHIC MAPPING OF PULMONARY NK1 AND NK2 TACHYKININ RECEPTORS AND CHANGES AFTER REPEATED ANTIGEN CHALLENGE IN GUINEA-PIGS

An autoradiographic technique was used to study the distribution of ch anges in pulmonary NK1 and NK2 receptors in guinea pig lung after repe ated antigen challenge. Specific labeling of [H-3]CP96345 (NK1 recepto rs) and [H-3]SR48968 (NK2 receptors) was localized over the cached and bronchial smooth muscle; the density of binding increased towards sma ller airways with a higher density for [H-3]CP96345 binding. Bronchial epithelium and pulmonary blood vessels were also labeled densely with [H-3]CP96345. No remarkable difference in the pattern of distribution of pulmonary NK1 and NK2 tachykinin receptors was observed between co ntrol, vehicle-challenged, and repeatedly antigen-challenged (weekly f or three times) guinea pigs. A significant reduction in specific label ing of [H-3]CP96345 (p < 0.01) and [H-3]SR48968 (p < 0.05) over pulmon ary structures was observed in antigen-challenged compared to control or vehicle-challenged animals. This study provides evidence that NK1 a nd NK2 tachykinin receptors are both localized to smooth muscle of all sizes in guinea pig airways and provides further evidence for a discr ete distribution of NK1 and NK2 tachykinin receptors, consistent with their relative functional activities. In an established model of airwa y inflammation a decrease in the expression of NK1 and NK2 tachykinin receptors was evident on several different cell types within the lung, and this could influence airway and vascular reactivity. Copyright (C ) 1996 Elsevier Science Inc.