Cosecretion of calcitonin and calcitonin gene-related peptide from cultured rat medullary thyroid C cells.

Whether C cells cosecrete calcitonin (CT) and CGRP was examined by exposing cultured rat medullary thyroid carcinoma 6-23 cells for 2 h to high medium Ca and to agents with a potential for affecting Ca-dependent secretion. In every experiment exposure of cells to high medium Ca (2.0-2.5 mM) provoked an increased release of both peptides that was highly correlated (r = 0.73). With other test substances, also, changes in both hormones occurred in parallel. The Ca-channel activator, BAY-K-8644 (10 microM) increased secretion, and this was inhibited by the Ca channel blocker, nitrendipine (10 microM). The Ca2+ ionophore, ionomycin (5 microM), increased release, and the calmodulin-Ca channel inhibitor, phenytoin (100 microM), inhibited Ca-induced release. The active 4 beta isomer of phorbol-12,13-didecanoate (0.1 microM), but not the inactive 4 alpha isomer, increased secretion. The findings suggest that pathways mediating C cell secretion include plasma membrane Ca channels, intracellular [Ca2+], calmodulin, and protein kinase C. The results show that the secretory process in rat C cells involves the release of CGRP as well as CT.