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Purinergic agonists stimulate the secretion of endothelin‐1 in rat thyroid FRTL‐5 cells
Author(s) -
Vainio Minna,
Saijonmaa Outi,
Fyhrquist Frej,
Törnquist Kid
Publication year - 1996
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/(sici)1097-4652(199612)169:3<538::aid-jcp14>3.0.co;2-1
Subject(s) - purinergic receptor , secretion , thyroid , endocrinology , chemistry , endothelin receptor , microbiology and biotechnology , medicine , pharmacology , biology , receptor , adenosine
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 P 1 ‐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 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 chelator BAPTA or inhibition of calcium entry with Ni 2+ 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 P 1 ‐receptor pathway which is modulated by several signal transduction mechanisms including cAMP, Ca 2+ , and PKC. © 1996 Wiley‐Liss, Inc.