Autoradiographic mapping of pulmonary NK1 and NK2 tachykinin receptors and changes after repeated antigen challenge in guinea pigs

Abstract

An autoradiographic technique was used to study the distribution of changes in pulmonary NK1 and NK2 receptors in guinea pig lung after repeated antigen challenge. Specific labeling of [3H] CP96345 (NK1 receptors and [3H] SR48968 (NK2 receptors) was localized over the tracheal and bronchial smooth muscle; the density of binding increased towards smaller airways with a higher density for [3H]CP96345 binding. Branchial epithelium and pulmonary blood vessels were also labeled densely with [3H] CP96345. No remarkable difference in the pattern of distribution of pulmonary NK1 and NK2 tachykinin receptors was observed between control, vehicle-challenged, and repeatedly antigen-challenged (weekly for three times) guinea pigs. A significant reduction in specific labeling of [3H] CP96345 (p < 0.01) and [3H]SR48968 (P < 0.05) over pulmonary structures was observed in antigen-challenged compared to control or vehicle-challenged animals. This study provides evidence that NK1 and NK2 tachykinin receptors are both localized to smooth muscle of all sizes in guinea pig airways and provides further evidence for a discrete distribution of NK1 and NK2 tachykinin receptors, consistent with their relative functional activities. In an established model of airway 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.