Increased intracellular levels of calcitonin gene‐related peptide‐like immunoreactivity in pulmonary endocrine cells of hypoxic rats

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Abstract
The mammalian respiratory tract contains innervated groups of endocrine cells which are believed to respond to hypoxia. We have demonstrated the involvement of a specific regulatory peptide produced by the cells, calcitonin generelated peptide (CGRP), in this response. Cells immunoreactive for CGRP or for protein gene product 9·5 (PGP 9·5), a general marker of nerves and endocrine cells, were quantified in sections of lungs from hypoxic (21 days, 10 percent 02) and normoxic rats. An immunostaining method employing supra-optimal dilutions of primary antiserum was used. This detects variations in antigen concentration which may be masked if the routine, optimal dilution is used. The number of CGRP-immunoreactive endocrine cells was significantly (P < 0·001) greater in the lungs of hypoxic rats (76·9 ± 10·1 cells/cm2, mean ± SEM) compared with controls (19·7 ± 2·4). However, the numbers of PGP 9·5-immunoreactive cells were the same in both groups (81·3 ± 12·2, hypoxic; 79·5 ± 9·8 control), suggesting that the total number of endocrine cells did not change. It is concluded therefore that the apparent increase in CGRP-immunoreactive endocrine cells in hypoxic rat lungs is due to increased intracellular levels of the peptide. Since CGRP is a vasodilator, this could have important implications in the vasoconstrictor response to hypoxia.