Pulmonary calcitonin gene-related peptide immunoreactivity: nerve-endocrine cell interrelationships

Respiratory epithelium has been reported to be supplied with sensory nerves and to contain irritant and other receptors. In this immunohistochemical study, we examined the incidence, morphology, and distribution of calcitonin gene-related peptide (CGRP) immunoreactivity in epithelial cells the rat respiratory tract, using peroxidase anti-peroxidase (PAP) techniques. CGRP immunoreactivity was localized in capsaicin-sensitive nerve fibers and in capsaicin-nonsensitive endocrine cells occurring singly or in groups. These CGRP-immunoreactive structures reached close to or actually touched the airway lumen, were widely and abundantly present in the respiratory epithelium, and were arranged in distinct and characteristic patterns. CGRP-immunoreactive nerves innervated not only grouped cells but also single cells, and the innervation of these cells differed depending on whether they were in extrapulmonary or intrapulmonary epithelium. The specificity of the immunoreactivity was confirmed by absorption tests that excluded cross-reactivity with other peptides. The results suggest that epithelial nerve fibers and endocrine-like cells exhibiting CGRP immunoreactivity form a morphologic, and probably also a functional, complex throughout the respiratory epithelium. CGRP innervation may be related to receptor functions of respiratory epithelium.