Norepinephrine induced calcitonin secretion in rat medullary thyroid carcinoma 6—23 cells: Interaction between intracellular calcium and cAMP

Summary

Catecholamines are known to stimulate calcitonin secretion in C-cells by a receptor mediated pathway, but details regarding the postreceptor events are unknown. Since norepinephrine (NE) influences intracellular calcium concentration [Ca²⁺]_i and cAMP levels in C-cells, we used different adrenergic agonists and antagonists to investigate the effect of NE on [Ca²⁺]_i and cAMP accumulation, and on calcitonin secretion in rat MTC-6—23 cells. NE stimulated intracellular cAMP accumulation and calcitonin secretion dose-dependent, with 10⁻⁷ mol/1 causing maximal stimulation. The NE induced increase in cAMP accumulation/calcitonin secretion could be decreased to baseline by equimolar amounts of the β-adrenergic blocker propanolol. The a-blocker phentolamine did not significantly influence NE stimulated calcitonin secretion even at high concentrations. The β-adrenergic agonist fenoterol proved to be as effective as NE in stimulating cAMP accumulation/ calcitonin secretion. Activation of inhibitory G-proteins by the adenosine Al receptor analogue N6-phenyliso-propyladenosine at 10⁻⁶ mol/1 completely blocked NE stimulated calcitonin secretion. NE stimulated calcitonin secretion was also completely blocked by the cAMP antagonist RpcAMPs. The calcium channel blocker verapamil significantly inhibited NE stimulated calcitonin secretion, but interestingly increased NE stimulated cAMP accumulation. We conclude that NE induced calcitonin secretion is mediated through β-receptors coupled to adenylate cyclase via G-proteins. cAMP and changes in [Ca²⁺]_i are necessary for NE induced calcitonin secretion. There seems to be a complex interaction between the two pathways even regarding events occurring distal to cell membrane.

Key words

Norepinephrine - calcitonin secretion - C-cells - cAMP - intracellular calcium