PURINERGIC AGONISTS STIMULATE THE SECRETION OF ENDOTHELIN-1 IN RAT-THYROID FRTL-5 CELLS

The aim of the present study was to investigate the mechanisms regulat ing endothelin-1 (ET-1) secretion in rat thyroid FRTL-5 cells. ET-1 wa s found to be secreted after stimulation with adenosine and ATP. The r elease of ET-1 was sensitive to pertussis toxin, indicating a role of G-proteins in the stimulus-secretion coupling. The stimulation evoked by ATP or adenosine was inhibited by the P-1-receptor antagonist 8-cyc lopentyl-1,3-dipropylxanthine (DPCPX), and in the presence of adenosin e deaminase the adenosine- and ATP-mediated ET-1 secretion was abolish ed. These evidences suggest a role of a P-1-adenosine receptor in the secretion of ET-1. Increasing cyclic AMP with forskolin decreased the adenosine-mediated secretion. In addition, the intracellular calcium c helator BAPTA or inhibition of calcium entry with Ni2+ prevented the r esponse. Protein kinase C (PKC) is also partly involved in ET-1 secret ion in FRTL-5 cells. Activation of PKC with the phorbol ester phorbol 12-myristate 13-acetate (PMA) stimulated the secretion of ET-1 in a ti me- and dose-dependent manner. Furthermore, downregulation of PKC decr eased the secretion of ET-1 stimulated by adenosine. In conclusion, ET -1 secretion in FRTL-5 cells is stimulated via a pertussis toxin-sensi tive P-1-receptor pathway which is modulated by several signal transdu ction mechanisms including cAMP, Ca2+, and PKC. (C) 1996 Wiley-Liss, I nc.