Calcitonin gene-related peptide: endocrine distribution and characterization of circulating forms

This study reports the application of a highly sensitive and specific extraction-based radioimmunoassay for determining levels of calcitonin gene-related peptide (CGRP) in endocrine tissues and plasma of normal rats. In addition, we have characterized the immunoreactive material found in plasma using gel filtration and high performance liquid chromatography. The CGRP content of the thyroid was 100- to 1000-fold higher than that of the adrenals, pituitary or pancreas, while the gonads and kidneys contained appreciably smaller amounts of CGRP. There was no age- and sex-related difference in tissue content, with the exception of a subgroup of 450 g rats. These had a significantly raised thyroidal CGRP content compared to other rats of the same group. A significant correlation between thyroidal content and plasma levels was noted only in old (450 g) rats. CGRP-like immunoreactivity in plasma pooled from young adult (150 g) rats was found to be heterogeneous. Only 8% of the total immunoreactivity recovered from a Sephadex G50 column was found to coelute with synthetic rat CGRP when freeze-dried plasma was chromatographed and a significantly greater proportion (approximately 67%) eluted in the void volume. The void volume peak was markedly reduced when acid-methanol extracts of plasma were chromatographed under similar conditions. A major proportion of the immunoreactive material co-eluting with synthetic CGRP on gel filtration was also found to elute at a position corresponding to the monomer on HPLC: this was consistent with, though not proof of, structural identity.