Further evidence for the origin of circulating calcitonin gene-related peptide in the rat.

1. We have attempted to determine the origin of a potent circulating vasodilator, calcitonin gene-related peptide (CGRP), by assessing the effects of administration of capsaicin and colchicine, and of thyroidectomy on plasma levels. Plasma CGRP, neurokinin A and calcitonin levels were measured using highly sensitive and specific radioimmunoassays, and the circulating forms of CGRP characterized by size-exclusion gel and high-performance liquid chromatography. 2. Seven minutes following the intraperitoneal injection of capsaicin (10 mg/kg body weight) plasma CGRP and neurokinin A levels were found to rise by 15- and 4-fold respectively, while there was no change in circulating calcitonin levels. Chromatography revealed that the immunochemical forms of CGRP released into the circulation by capsaicin were similar to those found in normal plasma, which included a peak co-eluting with the intact CGRP molecule. 3. Six hours after the intraperitoneal administration of colchicine (10 mg/kg body weight), CGRP was not detectable in the circulation of 40-day-old rats and plasma levels were significantly lowered in the group of greater than or equal to 200-day-old rats. Chromatography revealed that peaks of circulating immunoreactivity corresponding to monomeric CGRP and its fragments were substantially reduced following colchicine treatment. 4. The magnitude of capsaicin-evoked elevation of plasma CGRP was only marginally (significant at 0.1 greater than P greater than 0.05) reduced by pre-treatment with colchicine. 5. Thyroidectomy alone caused a significant reduction of plasma CGRP levels in greater than or equal to 200-day-old rats; a greater reduction was observed when thyroidectomy was combined with colchicine administration. However, when 40-day-old rats were thyroidectomized, there was an unexplained elevation of plasma CGRP levels. 6. The results suggest that while CGRP is normally released into the circulation from nerve terminals, both in young adult (40-day-old) and old (greater than or equal to 200-day-old) animals, a thyroidal origin is obvious only in old rats.