Receptors for endothelin in cultured human thyroid cells and inhibition by endothelin of thyroglobulin secretion.

Abstract

Specific receptors for endothelin-1 (ET), a newly described vasoconstrictor peptide isolated from endothelium, have been identified in endocrine tissues such as hypothalamus, adrenal and pituitary. ET binding or action, not previously described in thyroid, were explored in this study. ET binding in cultured human thyrocytes was assayed at 4 C, 25 C, and 37 C, for 0.5-6 h with [125I]ET (0.1 nmol/L), and nonspecific binding estimated by coincubation with unlabeled ET (100 nmol/L). At 4 C, maximum specific binding was reached after 4 h; at 25 C and 37 C, specific binding increased in a time-dependent manner over 6 h with increased binding obtained at higher temperature. At 37 C after 2 h, 11% specific bound ET localized to surface membranes with 89% internalized. Scatchard analysis of surface membrane binding at 4 C for 4 h showed high affinity single class ET receptor (Kd = 0.20 nmol/L) and binding capacity of 4045 sites per cell. ET binding to thyroid cells had no effect on production of cAMP or cGMP. ET (0.1 nmol/L) significantly (P less than 0.001) inhibited thyroglobulin release from thyroid cells after 6 days with no effect on thymidine incorporation. Thus, we have identified specific receptors for endothelin in human thyrocytes, and an inhibitory action of the peptide on thyroglobulin release which is mediated by a noncyclic nucleotide mechanism.