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.
Seitz
P K
PK
Department of Pharmacology and Toxicology, University of Texas Medical Branch, Galveston, TX 77550.
Cooper
C W
CW
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology; D000818:Animals; D002116:Calcitonin / Q000378:metabolism*; D015740:Calcitonin Gene-Related Peptide; D009479:Neuropeptides / Q000378:metabolism*; D009568:Nitrendipine / Q000494:pharmacology; D010672:Phenytoin / Q000494:pharmacology; D010703:Phorbol Esters / Q000494:pharmacology; D051381:Rats; D013964:Thyroid Neoplasms / Q000378:metabolism*; D014268:Trifluoperazine / Q000494:pharmacology; D014407:Tumor Cells, Cultured / Q000378:metabolism; D014665:Vasodilator Agents / Q000378:metabolism*
D009479:Neuropeptides; D010703:Phorbol Esters; D014665:Vasodilator Agents; D014268:Trifluoperazine; C008876:phorbol-12,13-didecanoate; D010672:Phenytoin; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D002116:Calcitonin; D009568:Nitrendipine; D015740:Calcitonin Gene-Related Peptide