Expression and Distribution of Vasoactive Intestinal Polypeptide Receptor VPAC2 mRNA in Human Airways

Abstract

SUMMARY:Vasoactive intestinal polypeptide (VIP) is a putative neurotransmitter of the inhibitory non-adrenergic noncholinergic nervous system and influences many aspects of mammalian airway function. VIP binds to two G-protein-coupled 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 and cytochemical techniques, we studied the distribution of the mRNA that encodes the inducible receptor subtype VPAC 2 in the human respiratory tract. Northern blots demonstrated the expression of VPAC 2 mRNA in human airways 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 hybridization. In larger airways, positive VPAC 2 mRNA signals were localized to tracheal and bronchial ciliated epithelial cells. There was also marked staining of mucous and serous cells of submucosal glands. No signals were obtained in airway and vascular smooth muscle myocytes and endothelial cells. In peripheral lung tissues, VPAC 2 mRNA expression was localized to epithelial cells of the bronchioles. Specific staining was detected in immune cells and alveolar macrophages. In summary, VPAC 2 is localized in airway epithelial, 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 muscle myocytes may indicate that the effects of VIP on vasodilation and bronchodilation are mediated by VPAC 1 or undefined receptors. However, a paracrine modulation of the two most prominent effects of VIP in the respiratory tract by VPAC 2 cannot be excluded. (Lab Invest 2001, 81:749 -755).T he 28-amino acid vasoactive intestinal polypeptide (VIP) is a putative neurotransmitter or neuromodulator of the inhibitory non-adrenergic noncholinergic nervous system in mammalian airways (Maggi et al, 1995). VIP-immunoreactivity (VIP-IR) is present in cells of the tracheobronchial smooth muscle layer, in the walls of pulmonary and bronchial vessels, around submucosal glands, in the lamina propria, and in pulmonary ganglia (Dey et al, 1981;Lundberg et al, 1984). VIP-IR nerve fibers are found as branching networks in the respiratory tract (Ghatei et al, 1982) They decrease in frequency as the airways become smaller but extend to peripheral bronchioles (Lundberg et al, 1984). The pattern of VIPergic nerves largely follows that of cholinergic nerves (Laitinen et al, 1985). VIP-IR is also present in sensory nerves (Lundberg et al, 1984;Luts and Sundler, 1989).Several studies using receptor binding techniques have been performed to demonstrate the presence of VIP receptors and have shown abundant binding in different parts of the lungs Robberecht et al, 1981Robberecht et al, , 1988. Two types of VIP receptors have been cloned and characterized in the past years. They were termed the VPAC 1 receptor, formerly described as the VIP 1 receptor (Ishihara et a...

The Significance of Vasoactive Intestinal Peptide in Immunomodulation

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