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 regulating endothelin-1 (ET-1) secretion in rat thyroid FRTL-5 cells. ET-1 was found to be secreted after stimulation with adenosine and ATP. The release 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 P1-receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX), and in the presence of adenosine deaminase the adenosine- and ATP-mediated ET-1 secretion was abolished. These evidences suggest a role of a P1-adenosine receptor in the secretion of ET-1. Increasing cyclic AMP with forskolin decreased the adenosine-mediated secretion. In addition, the intracellular calcium chelator BAPTA or inhibition of calcium entry with Ni2+ prevented the response. Protein kinase C (PKC) is also partly involved in ET-1 secretion 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 time- and dose-dependent manner. Furthermore, downregulation of PKC decreased the secretion of ET-1 stimulated by adenosine. In conclusion, ET-1 secretion in FRTL-5 cells is stimulated via a pertussis toxin-sensitive P1-receptor pathway which is modulated by several signal transduction mechanisms including cAMP, Ca2+, and PKC.
Vainio
M
M
Department of Biosciences, University of Helsinki, Finland.
Saijonmaa
O
O
Fyhrquist
F
F
Törnquist
K
K
D000241:Adenosine / Q000494:pharmacology*; D000243:Adenosine Deaminase / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000502:physiology; D002460:Cell Line; D000242:Cyclic AMP / Q000502:physiology; D006152:Cyclic GMP / Q000502:physiology; D019332:Endothelin-1 / Q000378:metabolism*; D004789:Enzyme Activation; D009569:Nitric Oxide / Q000502:physiology; D011493:Protein Kinase C / Q000502:physiology; D058906:Purinergic P1 Receptor Agonists; D051381:Rats; D018047:Receptors, Purinergic P1 / Q000502:physiology; D012636:Secretory Rate / Q000187:drug effects; D015398:Signal Transduction; D013961:Thyroid Gland; D014970:Xanthines / Q000494:pharmacology
D019332:Endothelin-1; D058906:Purinergic P1 Receptor Agonists; D018047:Receptors, Purinergic P1; D014970:Xanthines; D009569:Nitric Oxide; D000255:Adenosine Triphosphate; C051360:1,3-dipropyl-8-cyclopentylxanthine; D000242:Cyclic AMP; D011493:Protein Kinase C; D000243:Adenosine Deaminase; D006152:Cyclic GMP; D000241:Adenosine; D002118:Calcium