Adenosine A1-receptors inhibit cAMP and Ca2+ mediated calcitonin secretion in C-cells

The effect of the adenosine A1 receptor activation on calcitonin secretion was studied in medullary thyroid carcinoma cells of the rat (rMTC 6-23). Calcitonin was determined by radioimmunoassay, intracellular cAMP by protein binding assay, intracellular calcium in fura-2 loaded single cells using microspectrofluorimetry, and calcium channel activity by patch clamp technique. The adenosine A1 receptor analogue N-6 phenylisopropyl-adenosine (PIA) (10(-10)-10(-6) M) inhibits dose-dependently glucagon (10(-7) M) and rGRH (10(-7) M) stimulated cAMP formation and calcitonin secretion. These effects were partly abolished by pretreatment with pertussis toxin (PT) (100 ng/ml). PIA (10(-10)-10(-6) M) also suppressed extracellular calcium-stimulated calcitonin secretion, rises in intracellular calcium, and calcium channel currents. PT (100 ng/ml) pretreatment again partly abolished this inhibitory effect. The addition to the medium of adenosine deaminase (0.4 U/ml) stimulated calcitonin secretion. Our results suggest that in calcitonin-secreting cells A1 receptors couple to adenylate cyclase and calcium channels via PT-sensitive G proteins and thus inhibit calcitonin secretion. Adenosine seems to act as an autocrine/paracrine factor in calcitonin-secreting cells.