NOREPINEPHRINE-INDUCED CALCITONIN SECRETION IN RAT MEDULLARY-THYROID CARCINOMA-6-23 CELLS - INTERACTION BETWEEN INTRACELLULAR CALCIUM AND CAMP

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 intracellula r calcium concentration [Ca2+](i) and cAMP levels in C-cells, we used different adrenergic agonists and antagonists to investigate the effec t of NE on [Ca2+](i) and cAMP accumulation, and on calcitonin secretio n in rat MTC-6-23 cells. NE stimulated intracellular cAMP accumulation and calcitonin secretion dose-dependent, with 10(-7) mol/l causing ma ximal stimulation. The NE induced increase in cAMP accumulation/calcit onin secretion could be decreased to baseline by equimclar amounts of the beta-adrenergic blocker propanolol. The alpha-blocker phentolamine did not significantly influence NE stimulated calcitonin secretion ev en at high concentrations. The beta-adrenergic agonist fenoterol prove d to be as effective as NE in stimulating cAMP accumulation/ calcitoni n secretion. Activation of inhibitory G-proteins by the adenosine A1 r eceptor analogue N6-phenylisopropyladenosine at 10(-6) mol/l completel y 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 stim ulated calcitonin secretion, but interestingly increased NE stimulated cAMP accumulation. We conclude that NE induced calcitonin secretion i s mediated through beta-receptors coupled to adenylate cyclase via G-p roteins. cAMP and changes in [Ca2+](i) are necessary for NE induced ca lcitonin secretion. There seems to be a complex interaction between th e two pathways even regarding events occurring distal to cell membrane .