Expression and distribution of vasoactive intestinal polypeptide receptor VPAC(2) mRNA in human airways

Vasoactive intestinal polypeptide (VIP) is a putative neurotransmitter of t he inhibitory non-adrenergic noncholinergic nervous system and influences m any aspects of mammalian airway function. VIP binds to two G-protein-couple d VPAC receptors that are highly homologous structurally but distinguished by their different affinities for peptide analogues of VIP. As VIP binding sites in the respiratory tract have only been examined by ligand binding an d cytochemical techniques, we studied the distribution of the mRNA that enc odes the inducible receptor subtype VPAC(2) in the human respiratory tract. Northern blots demonstrated the expression of VPAC(2) mRNA in human airway s and other tissues. A human-specific VPAC(2) cRNA probe was used to detect VPAC(2) mRNA expression in human lung by nonradioactive in situ hybridizat ion. In larger airways, positive VPAC(2) mRNA signals were localized to tra cheal and bronchial ciliated epithelial cells. There was also marked staini ng of mucous and serous cells of submucosal glands. No signals were obtaine d in airway and vascular smooth muscle myocytes and endothelial cells. In p eripheral lung tissues, VPAC(2) mRNA expression was localized to epithelial cells of the bronchioles. Specific staining was detected in immune cells a nd alveolar macrophages. In summary, VPAC(2) is localized in airway epithel ial, glandular, and immune cells of the lung but not in airway and vascular smooth muscle. The absence of VPAC(2) mRNA in vascular and airway smooth m uscle myocytes may indicate that the effects of VIP on vasodilation and bro nchodilation are mediated by VPAC(1) or undefined receptors. However, a par acrine modulation of the two most prominent effects of VIP in the respirato ry tract by VPAC(2) cannot be excluded.