Regulation of calcitonin secretion in vitro

The concentration of extracellular calcium rightly regulates calcitonin secretion by calcium influx through dihydropyridine-sensitive voltage-dependent calcium channels; the result is an increase in intracellular calcium. There also exists a cAMP-dependent pathway of calcitonin release activated by glucagon or growth hormone releasing hormone. In thyroid C-cells, as in all cells, there is dual regulation of adenylate cyclase, mediated by inhibitory or stimulatory G proteins; glucagon stimulated cAMP production can be inhibited by somatostatin via pertussis toxin sensitive inhibitory G proteins. Somatostatin inhibits not only cAMP dependent but also calcium-dependent calcitonin secretion. Furthermore, somatostatin inhibits voltage dependent calcium channel currents thereby lowering cytosolic calcium. These actions also involve a pertussis toxin-sensitive inhibitory G protein but they occur independently of changes in the cytosolic cAMP concentration. Thus multiple interactions between second messenger systems at different cellular levels modulate calcitonin secretion.